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135-548: The USAN Program states that its goal is to select simple, informative, and unique nonproprietary names (also called generic names) for drugs by establishing logical nomenclature classifications based on pharmacological or chemical relationships. In addition to drugs, the USAN Council names agents for gene therapy and cell therapy, contact lens polymers , surgical materials, diagnostics, carriers, and substances used as an excipient . The USAN Council works in conjunction with

270-461: A form of gene augmentation where new gene is added, may improve a cells function without modifying the genes that cause a disorder. Gene therapy may be classified into two types by the type of cell it affects: somatic cell and germline gene therapy. In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete , germ cell , gametocyte , or undifferentiated stem cell . Any such modifications affect

405-455: A retrovirus , can modify a cell's nuclear genome to permanently express a gene, although vectors can be modified to prevent integration. Retroviruses were used in 18% of trials before 2018. Libmeldy is an ex vivo stem cell treatment for metachromatic leukodystrophy which uses a lentiviral vector and was approved by the European medical agency in 2020. Adeno-associated virus (AAV)

540-581: A therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA was performed in 1980, by Martin Cline , but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health , was performed in May 1989. The first therapeutic use of gene transfer as well as

675-580: A " Special Relationship " with the United Kingdom and strong ties with Canada , Australia , New Zealand , the Philippines , Japan , South Korea , Israel , and several European Union countries ( France , Italy , Germany , Spain , and Poland ). The U.S. works closely with its NATO allies on military and national security issues, and with countries in the Americas through

810-447: A cancer cell to die. Another approach is the use oncolytic viruses , such as Oncorine, which are viruses that selectively reproduce in cancerous cells leaving other cells unaffected. mRNA has been suggested as a non-viral vector for cancer gene therapy that would temporarily change a cancerous cell's function to create antigens or kill the cancerous cells and there have been several trials. Afamitresgene autoleucel , sold under

945-546: A cell without permanently altering the cell's nuclear genome. These vectors can be used to cause antigens to be added to cancers causing an immune response, or hinder angiogenesis by expressing certain proteins. An Adenovirus vector is used in the commercial products Gendicine and Oncorine . Another commercial product, Rexin G , uses a retrovirus-based vector and selectively binds to receptors that are more expressed in tumors. One approach, suicide gene therapy , works by introducing genes encoding enzymes that will cause

1080-466: A cell's genetic expression with genetic material that is not integrated into the host cell's DNA. As of 2017, such vectors were used in 20% of trials for gene therapy. Adenovirus vectors are mostly used in cancer treatments and novel genetic vaccines such as the Ebola vaccine , vaccines used in clinical trials for HIV and SARS-CoV-2 , or cancer vaccines . Lentiviral vectors based on lentivirus ,

1215-480: A cell. Fact-checkers , such as Full Fact , Reuters , PolitiFact , and FactCheck.org said that calling the vaccines a gene therapy was incorrect. Podcast host Joe Rogan was criticized for calling mRNA vaccines gene therapy as was British politician Andrew Bridgen , with fact checker Full Fact calling for Bridgen to be removed from the conservative party for this and other statements. Gene therapy encapsulates many forms of adding different nucleic acids to

1350-402: A cell. Gene augmentation adds a new protein coding gene to a cell. One form of gene augmentiation is gene replacement therapy , a treatment for monogenic recessive disorders where a single gene is not functional an additional functional gene is added. For diseases caused by multiple genes or a dominant gene, gene silencing or gene editing approaches are more appropriate but gene addition,

1485-412: A chimeric antigen receptor. In vivo gene therapy is seen as simpler, since it does not require the harvesting of mitotic cells. However, ex vivo gene therapies are better tolerated and less associated with severe immune responses. The death of Jesse Gelsinger in a trial of an adenovirus -vectored treatment for ornithine transcarbamylase deficiency due to a systemic inflammatory reaction led to

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1620-474: A chromosome and returning the transformed cells to patients. Gene editing is a potential approach to alter the human genome to treat genetic diseases, viral diseases, and cancer. As of 2020 these approaches are being studied in clinical trials. In 1986, a meeting at the Institute Of Medicine defined gene therapy as the addition or replacement of a gene in a targeted cell type. In

1755-542: A coordinated, continent-wide military effort. Finally, deteriorating relations between the British military establishment and the colonists, relations that were already less than positive, set the stage for further distrust and dislike of British troops. Following their victory in the French and Indian War, Britain began to assert greater control over local colonial affairs, resulting in colonial political resistance ; one of

1890-405: A copy of this gene that does not contain the deleterious mutation and thereby produces a functional protein. This strategy is referred to as gene replacement therapy and could be employed to treat inherited retinal diseases. While the concept of gene replacement therapy is mostly suitable for recessive diseases, novel strategies have been suggested that are capable of also treating conditions with

2025-534: A decentralized government that operated until 1789. After the British surrender at the siege of Yorktown in 1781 American sovereignty was internationally recognized by the Treaty of Paris (1783), through which the U.S. gained territory stretching west to the Mississippi River, north to present-day Canada, and south to Spanish Florida . The Northwest Ordinance (1787) established the precedent by which

2160-496: A defect in lipoprotein lipase . DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein. Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome . Naked DNA approaches have also been explored, especially in the context of vaccine development. Generally, efforts focused on administering

2295-731: A dominant pattern of inheritance. In vivo, gene editing systems using CRISPR have been used in studies with mice to treat cancer and have been effective at reducing tumors. In vitro, the CRISPR system has been used to treat HPV cancer tumors. Adeno-associated virus , Lentivirus based vectors have been to introduce the genome for the CRISPR system. The delivery of DNA into cells can be accomplished by multiple methods . The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods). In order to replicate , viruses introduce their genetic material into

2430-407: A few prominent industrialists , largely by their formation of trusts and monopolies to prevent competition. Tycoons led the nation's expansion in the railroad , petroleum , and steel industries. The United States emerged as a pioneer of the automotive industry . These changes were accompanied by significant increases in economic inequality , slum conditions , and social unrest , creating

2565-723: A functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a " vector ", which carries the molecule inside cells. Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers' attention, although as of 2014 , it was still largely an experimental technique. These include treatment of retinal diseases Leber's congenital amaurosis and choroideremia , X-linked SCID , ADA-SCID, adrenoleukodystrophy , chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), multiple myeloma , haemophilia , and Parkinson's disease . Between 2013 and April 2014, US companies invested over $ 600 million in

2700-412: A gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR . The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing

2835-565: A general rule, the application for a USAN should be forwarded to the USAN Council after the Investigational New Drug (IND) is active and clinical trials have begun. Many drug manufacturers seeking a USAN are multinational companies with subsidiaries in various parts of the world or contractual agreements with drug firms outside the United States . Therefore, it is highly desirable to the pharmaceutical company ,

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2970-506: A genetic condition, and Zolgensma for the treatment of spinal muscular atrophy both use an adeno-associated virus vector. United States The United States of America ( USA ), commonly known as the United States ( U.S. ) or America , is a country primarily located in North America . It is a federal union of 50 states and a federal capital district, Washington, D.C. The 48 contiguous states border Canada to

3105-487: A genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages. In germline gene therapy (GGT), germ cells ( sperm or egg cells ) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism's cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and

3240-666: A global reach. The U.S. is a founding member of the World Bank , Organization of American States , NATO , and the United Nations , as well as a permanent member of the UN Security Council . The first documented use of the phrase "United States of America" is a letter from January 2, 1776. Stephen Moylan , a Continental Army aide to General George Washington , wrote to Joseph Reed , Washington's aide-de-camp , seeking to go "with full and ample powers from

3375-402: A healthy gene have been proposed and are being studied for treating some genetic diseases. As of 2017, 11.1% of gene therapy clinical trials targeted monogenic diseases. Diseases such as sickle cell disease that are caused by autosomal recessive disorders for which a person's normal phenotype or cell function may be restored in cells that have the disease by a normal copy of the gene that

3510-446: A micropipette directly into a living mammalian cell, and exposing cells to a precipitate of DNA that contained the desired genes. Scientists theorized that a virus could also be used as a vehicle, or vector, to deliver new genes into cells. One of the first scientists to report the successful direct incorporation of functional DNA into a mammalian cell was biochemist Dr. Lorraine Marquardt Kraus (6 September 1922 – 1 July 2016) at

3645-439: A number of laboratories are working on delivery of PEGylated particles, which form serum protein coronas and chiefly exhibit LDL receptor mediated uptake in cells in vivo . There have been attempts to treat cancer using gene therapy. As of 2017, 65% of gene therapy trials were for cancer treatment. Adenovirus vectors are useful for some cancer gene therapies because adenovirus can transiently insert genetic material into

3780-457: A patient themselves, but include ex vivo approaches, and would not depend on the vector used. During the COVID-19 pandemic, some academics insisted that the mRNA vaccines for COVID were not gene therapy to prevent the spread of incorrect information that the vaccine could alter DNA, other academics maintained that the vaccines were a gene therapy because they introduced genetic material into

3915-405: A patient's genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients. Gene therapy was first conceptualized in the 1960s, when the feasibility of adding new genetic functions to mammalian cells began to be researched. Several methods to do so were tested, including injecting genes with

4050-598: A period of heightened, overt racism following Reconstruction, a time often called the nadir of American race relations . A series of Supreme Court decisions, including Plessy v. Ferguson , emptied the Fourteenth and Fifteenth Amendments of their force, allowing Jim Crow laws in the South to remain unchecked, sundown towns in the Midwest, and segregation in communities across the country , which would be reinforced by

4185-413: A potential application of AAV gene therapy for human disease. Non-viral vectors for gene therapy present certain advantages over viral methods, such as large scale production and low host immunogenicity . However, non-viral methods initially produced lower levels of transfection and gene expression , and thus lower therapeutic efficacy. Newer technologies offer promise of solving these problems, with

United States Adopted Name - Misplaced Pages Continue

4320-488: A prominent leader in the early 1960s. The Great Society plan of President Lyndon Johnson 's administration resulted in groundbreaking and broad-reaching laws, policies and a constitutional amendment to counteract some of the worst effects of lingering institutional racism . The counterculture movement in the U.S. brought significant social changes, including the liberalization of attitudes toward recreational drug use and sexuality . It also encouraged open defiance of

4455-526: A sense of manifest destiny . The Missouri Compromise attempted to balance the desire of northern states to prevent the expansion of slavery into new territories with that of southern states to extend it, admitting Missouri as a slave state and Maine as a free state. It further prohibited slavery in all other lands of the Louisiana Purchase north of the 36°30′ parallel . As Americans expanded further into land inhabited by Native Americans,

4590-614: A sense of American identity as well. Men who otherwise never left their own colony now traveled across the continent to fight alongside men from decidedly different backgrounds but who were no less "American". British officers trained American officers for battle, most notably George Washington ; these officers would lend their skills and expertise to the colonists' cause during the American Revolutionary War to come. In addition, colonial legislatures and officials found it necessary to cooperate intensively in pursuit of

4725-584: A success was demonstrated in a trial that started on 14 September 1990, when Ashanthi DeSilva was treated for ADA - SCID . The first somatic treatment that produced a permanent genetic change was initiated in 1993. The goal was to cure malignant brain tumors by using recombinant DNA to transfer a gene making the tumor cells sensitive to a drug that in turn would cause the tumor cells to die. The polymers are either translated into proteins , interfere with target gene expression , or possibly correct genetic mutations . The most common form uses DNA that encodes

4860-416: A temporary blueprint that degrades naturally, as in a non-integrative vectors , or to enter the host's nucleus becoming a permanent part of the host's nuclear DNA in infected cells. A number of viruses have been used for human gene therapy, including viruses such as lentivirus , adenoviruses , herpes simplex , vaccinia , and adeno-associated virus . Adenovirus viral vectors (Ad) temporarily modify

4995-467: A temporary halt on gene therapy trials across the United States. As of 2021 , in vivo and ex vivo therapeutics are both seen as safe. The concept of gene therapy is to fix a genetic problem at its source. If, for instance, a mutation in a certain gene causes the production of a dysfunctional protein resulting (usually recessively) in an inherited disease, gene therapy could be used to deliver

5130-401: A year). Juvenile correctional facilities are operated by local or state governments and serve as longer-term placements for any minor adjudicated as delinquent and ordered by a judge to be confined. As of January 2023, the United States has the sixth-highest per capita incarceration rate in the world—531 people per 100,000 inhabitants—and the largest prison and jail population in

5265-408: Is a virus that is incapable of transmission between cells unless the cell is infected by another virus, a helper virus. Adenovirus and the herpes viruses act as helper viruses for AAV. AAV persists within the cell outside of the cell's nuclear genome for an extended period of time through the formation of concatemers mostly organized as episomes . Genetic material from AAV vectors is integrated into

5400-591: Is believed to be the first widespread culture in the Americas. Over time, indigenous North American cultures grew increasingly sophisticated, and some, such as the Mississippian culture , developed agriculture , architecture , and complex societies . In the post-archaic period , the Mississippian cultures were located in the midwestern , eastern , and southern regions, and the Algonquian in

5535-405: Is introduced to the patient, which then achieves the desired biological effect by passing the genetic material (e.g. for a missing protein) into the patient's cells. In ex vivo gene therapies, such as CAR-T therapeutics, the patient's own cells (autologous) or healthy donor cells (allogeneic) are modified outside the body (hence, ex vivo ) using a vector to express a particular protein, such as

United States Adopted Name - Misplaced Pages Continue

5670-498: Is known as the presidential system , in contrast to the parliamentary system , where the executive is part of the legislative body. Many countries around the world imitated this aspect of the 1789 Constitution of the United States , especially in the Americas. The Constitution is silent on political parties. However, they developed independently in the 18th century with the Federalist and Anti-Federalist parties. Since then,

5805-431: Is mutated, may be a good candidate for gene therapy treatment. The risks and benefits related to gene therapy for sickle cell disease are not known. Gene therapy has been used in the eye . The eye is especially suitable for adeno-associated virus vectors. Voretigene neparvovec is an approved gene therapy to treat Leber's hereditary optic neuropathy . alipogene tiparvovec , a treatment for pancreatitis caused by

5940-688: Is nominated to the USAN Council annually by each sponsoring organization; the FDA nominates one liaison member annually. The member-at-large is selected by the sponsoring organizations from a list of candidates proposed by the AMA, APhA, and the USP. The five nominees to the Council must be approved annually by the board of trustees of the three sponsoring organizations. By definition, nonproprietary names are not subject to proprietary trademark rights but are entirely in

6075-438: Is now the United States experienced conflicts with Native Americans, they also engaged in trade, exchanging European tools for food and animal pelts. Relations ranged from close cooperation to warfare and massacres. The colonial authorities often pursued policies that forced Native Americans to adopt European lifestyles, including conversion to Christianity. Along the eastern seaboard, settlers trafficked African slaves through

6210-552: Is the federal agency charged with addressing most environmental-related issues . The idea of wilderness has shaped the management of public lands since 1964, with the Wilderness Act . The Endangered Species Act of 1973 provides a way to protect threatened and endangered species and their habitats. The United States Fish and Wildlife Service implements and enforces the Act. In 2024, the U.S. ranked 34th among 180 countries in

6345-603: The Allies of World War I , helping to turn the tide against the Central Powers . In 1920, a constitutional amendment granted nationwide women's suffrage . During the 1920s and '30s, radio for mass communication and the invention of early television transformed communications nationwide. The Wall Street Crash of 1929 triggered the Great Depression , which President Franklin D. Roosevelt responded to with

6480-553: The Atlantic slave trade . The original Thirteen Colonies that would later found the United States were administered as possessions of Great Britain , and had local governments with elections open to most white male property owners . The colonial population grew rapidly, eclipsing Native American populations; by the 1770s, the natural increase of the population was such that only a small minority of Americans had been born overseas. The colonies' distance from Britain allowed for

6615-817: The Bering land bridge more than 12,000 years ago, and formed various civilizations and societies . British colonization led to the first settlement of the Thirteen Colonies in Virginia in 1607. Clashes with the British Crown over taxation and political representation sparked the American Revolution , with the Second Continental Congress formally declaring independence on July 4, 1776. Following its victory in

6750-549: The Environmental Performance Index . The country joined the Paris Agreement on climate change in 2016 and has many other environmental commitments. The United States is a federal republic of 50 states and a separate federal capital district, Washington, D.C. It also asserts sovereignty over five unincorporated territories and several uninhabited island possessions . The U.S. is

6885-500: The Federal Bureau of Investigation (FBI) and the U.S. Marshals Service have national jurisdiction and specialized duties, such as protecting civil rights , national security and enforcing U.S. federal courts ' rulings and federal laws. State courts conduct most civil and criminal trials, and federal courts handle designated crimes and appeals of state court decisions . There is no unified "criminal justice system" in

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7020-720: The Great Lakes , Mississippi River and Gulf of Mexico . British colonization of the East Coast began with the Virginia Colony (1607) and Plymouth Colony (1620). The Mayflower Compact and the Fundamental Orders of Connecticut established precedents for representative self-governance and constitutionalism that would develop throughout the American colonies. While European settlers in what

7155-719: The Great Lakes region and along the Eastern Seaboard , while the Hohokam culture and Ancestral Puebloans inhabited the southwest . Native population estimates of what is now the United States before the arrival of European immigrants range from around 500,000 to nearly 10 million. Christopher Columbus began exploring the Caribbean for Spain in 1492, leading to Spanish-speaking settlements and missions from Puerto Rico and Florida to New Mexico and California . France established its own settlements along

7290-524: The House of Representatives , a lower house based on population; and the Senate , an upper house based on equal representation for each state. Federalism provides substantial autonomy to the 50 states, while the country's political culture promotes liberty , equality , individualism , personal autonomy , and limited government . One of the world's most developed countries , the United States has had

7425-596: The Midwest . At the same time, about one million French Canadians migrated from Quebec to New England . During the Great Migration , millions of African Americans left the rural South for urban areas in the North. Alaska was purchased from Russia in 1867. The Compromise of 1877 effectively ended Reconstruction and white supremacists took local control of Southern politics . African Americans endured

7560-460: The National Institutes of Health (NIH), Bethesda, in the United States successfully corrected genetic defects associated with Lesch-Nyhan syndrome , a debilitating neurological disease , by adding foreign DNA to cultured cells collected from patients suffering from the disease. The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation )

7695-688: The National Park Service and other agencies. About 28% of the country's land is publicly owned and federally managed, primarily in the Western States . Most of this land is protected , though some is leased for commercial use, and less than one percent is used for military purposes. Environmental issues in the United States include debates on non-renewable resources and nuclear energy , air and water pollution , biodiversity , logging and deforestation , and climate change . The U.S. Environmental Protection Agency (EPA)

7830-652: The New Deal , a series of sweeping programs and public works projects combined with financial reforms and regulations . All were intended to protect against future economic depressions. Initially neutral during World War II , the U.S. began supplying war materiel to the Allies of World War II in March 1941 and entered the war in December after the Empire of Japan 's attack on Pearl Harbor . The U.S. developed

7965-778: The Organization of American States and the United States–Mexico–Canada Free Trade Agreement . In South America, Colombia is traditionally considered to be the closest ally of the United States. The U.S. exercises full international defense authority and responsibility for Micronesia , the Marshall Islands , and Palau through the Compact of Free Association . It has increasingly conducted strategic cooperation with India , but its ties with China have steadily deteriorated. Since 2014,

8100-648: The Pentium microprocessor in accordance with Moore's law , rechargeable lithium-ion batteries , the first gene therapy trial, and cloning either emerged in the U.S. or were improved upon there. The Human Genome Project was formally launched in 1990, while Nasdaq became the first stock market in the United States to trade online in 1998. In the Gulf War of 1991, an American-led international coalition of states expelled an Iraqi invasion force that had occupied neighboring Kuwait . The September 11 attacks on

8235-534: The Soviet Union's collapse and the end of the Cold War in 1991, the U.S. emerged as the world's sole superpower , wielding significant geopolitical influence globally . The U.S. national government is a presidential constitutional federal republic and liberal democracy with three separate branches : legislative , executive , and judicial . It has a bicameral national legislature composed of

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8370-591: The Spanish–American War . (The Philippines was granted full independence from the U.S. on July 4, 1946, following World War II. Puerto Rico and Guam have remained U.S. territories.) American Samoa was acquired by the United States in 1900 after the Second Samoan Civil War . The U.S. Virgin Islands were purchased from Denmark in 1917. The United States entered World War I alongside

8505-537: The University of Tennessee Health Science Center in Memphis, Tennessee . In 1961, she managed to genetically alter the hemoglobin of cells from bone marrow taken from a patient with sickle cell anaemia . She did this by incubating the patient's cells in tissue culture with DNA extracted from a donor with normal hemoglobin . In 1968, researchers Theodore Friedmann , Jay Seegmiller, and John Subak-Sharpe at

8640-613: The World Health Organization (WHO) international nonproprietary name (INN) Expert Committee and national nomenclature groups to standardize drug nomenclature and establish rules governing the classification of new substances. The USAN Council began in June 1961 after the AMA and the USP jointly formed the AMA-USP Nomenclature Committee. The American Pharmacists Association (APhA) became

8775-700: The cotton gin made the institution increasingly profitable for Southern elites . This sectional conflict regarding slavery culminated in the American Civil War (1861–1865). Eleven slave states seceded and formed the Confederate States of America , while the other states remained in the Union . War broke out in April 1861 after the Confederates bombarded Fort Sumter . After

8910-537: The fall of communism and the collapse of the Soviet Union , which marked the end of the Cold War and left the United States as the world's sole superpower . The 1990s saw the longest recorded economic expansion in American history , a dramatic decline in U.S. crime rates , and advances in technology . Throughout this decade, technological innovations such as the World Wide Web , the evolution of

9045-445: The largest nominal GDP since about 1890 and accounted for over 15% of the global economy in 2023. It possesses by far the largest amount of wealth of any country and has the highest disposable household income per capita among OECD countries. The U.S. ranks among the world's highest in economic competitiveness , productivity , innovation , human rights , and higher education . Its hard power and cultural influence have

9180-495: The viral capsid , lower immunogenicity, ability to transduce both dividing and nondividing cells, the potential to integrate site specifically and to achieve long-term expression in the in-vivo treatment. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters. Not all medical procedures that introduce alterations to

9315-733: The 1775 Battles of Lexington and Concord , igniting the American Revolutionary War . At the Second Continental Congress , the colonies appointed George Washington commander-in-chief of the Continental Army , and created a committee that named Thomas Jefferson to draft the Declaration of Independence . Two days after passing the Lee Resolution to create an independent nation the Declaration

9450-408: The 1775–1783 Revolutionary War , the country continued to expand westward across North America , resulting in the dispossession of native inhabitants . As more states were admitted , a North–South division over slavery led to the secession of the Confederate States of America , which fought states remaining in the Union in the 1861–1865 American Civil War . With the victory and preservation of

9585-520: The 2010s, political polarization in the country increased between liberal and conservative factions. This polarization was capitalized upon in the January 2021 Capitol attack , when a mob of insurrectionists entered the U.S. Capitol and sought to prevent the peaceful transfer of power in an attempted self-coup d'état . The United States is the world's third-largest country by total area behind Russia and Canada. The 48 contiguous states and

9720-596: The American West have an alpine climate . The climate is arid in the Southwest, Mediterranean in coastal California , and oceanic in coastal Oregon , Washington , and southern Alaska . Most of Alaska is subarctic or polar . Hawaii , the southern tip of Florida and U.S. territories in the Caribbean and Pacific are tropical . States bordering the Gulf of Mexico are prone to hurricanes, and most of

9855-475: The Declaration of Independence on July 4, 1776. The term "United States" and the initialism "U.S.", used as nouns or as adjectives in English, are common short names for the country. The initialism "USA", a noun, is also common. "United States" and "U.S." are the established terms throughout the U.S. federal government , with prescribed rules. In English, the term "America" rarely refers to topics unrelated to

9990-573: The District of Columbia occupy a combined area of 3,119,885 square miles (8,080,470 km ). The coastal plain of the Atlantic seaboard gives way to inland forests and rolling hills in the Piedmont plateau region. The Appalachian Mountains and the Adirondack massif separate the East Coast from the Great Lakes and the grasslands of the Midwest . The Mississippi River System ,

10125-573: The Elder concluded that major military resources needed to be devoted to North America to win the war against France. For the first time, the continent became one of the main theaters of what could be termed a " world war ". The British colonies' position as an integral part of the British Empire became more apparent during the war, with British military and civilian officials becoming a more significant presence in American life. The war increased

10260-683: The January 1863 Emancipation Proclamation , many freed slaves joined the Union army . The war began to turn in the Union's favor following the 1863 Siege of Vicksburg and Battle of Gettysburg , and the Confederacy surrendered in 1865 after the Union's victory in the Battle of Appomattox Court House . The Reconstruction era followed the war. After the assassination of President Abraham Lincoln , Reconstruction Amendments were passed to protect

10395-569: The Journal of Law and the Biosciences, Sherkow et al. argued for a narrower definition of gene therapy than the FDA's in light of new technology that would consist of any treatment that intentionally and permanently modified a cell's genome, with the definition of genome including episomes outside the nucleus but excluding changes due to episomes that are lost over time. This definition would also exclude introducing cells that did not derive from

10530-463: The Netherlands prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations and higher risks versus SCGT. The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general). In in vivo gene therapy, a vector (typically, a virus)

10665-611: The Rocky Mountains, the Yellowstone Caldera , is the continent's largest volcanic feature. In 2021, the United States had 8% of global permanent meadows and pastures and 10% of cropland. With its large size and geographic variety, the United States includes most climate types. East of the 100th meridian , the climate ranges from humid continental in the north to humid subtropical in the south. The western Great Plains are semi-arid . Many mountainous areas of

10800-647: The U.S. has become a key ally of Ukraine ; it has also provided the country with significant military equipment and other support in response to Russia's 2022 invasion . The president is the commander-in-chief of the United States Armed Forces and appoints its leaders, the secretary of defense and the Joint Chiefs of Staff . The Department of Defense , which is headquartered at the Pentagon near Washington, D.C., administers five of

10935-661: The U.S. territories." Despite disparate systems of confinement, four main institutions dominate: federal prisons , state prisons , local jails, and juvenile correctional facilities . Federal prisons are run by the Federal Bureau of Prisons and hold people who have been convicted of federal crimes, including pretrial detainees. State prisons, run by the official department of correction of each state, hold sentenced people serving prison time (usually longer than one year) for felony offenses. Local jails are county or municipal facilities that incarcerate defendants prior to trial; they also hold those serving short sentences (typically under

11070-479: The USAN as the established name for labeling and advertising new single-entity drugs marketed in the United States. The AMA Council on Drugs no longer exists as a separate entity. The FDA now has a representative on the USAN Council, which has moved away from chemically derived names. Currently, the USAN Council has five members, one from each sponsoring organization, one from the FDA, and a member-at-large. One member

11205-464: The United States and the peaceful transfer of power , respectively. The Louisiana Purchase of 1803 from France nearly doubled the territory of the United States. Lingering issues with Britain remained , leading to the War of 1812 , which was fought to a draw. Spain ceded Florida and its Gulf Coast territory in 1819. In the late 18th century, American settlers began to expand westward , many with

11340-714: The United States entered the Cold War, where geopolitical tensions between the U.S. and the Soviet Union led the two countries to dominate world affairs . The U.S. utilized the policy of containment to limit the USSR's sphere of influence, and prevailed in the Space Race , which culminated with the first crewed Moon landing in 1969. Domestically, the U.S. experienced economic growth , urbanization , and population growth following World War II . The civil rights movement emerged, with Martin Luther King Jr. becoming

11475-666: The United States has operated as a de facto two-party system , though the parties in that system have been different at different times. The two main national parties are presently the Democratic and the Republican . The former is perceived as relatively liberal in its political platform while the latter is perceived as relatively conservative . In the American federal system , sovereign powers are shared between two levels of elected government: national and state. People in

11610-593: The United States in 2001 by the pan-Islamist militant organization al-Qaeda led to the war on terror , and subsequent military interventions in Afghanistan and Iraq . The cultural impact of the attacks was profound and long-lasting. The U.S. housing bubble culminated in 2007 with the Great Recession , the largest economic contraction since the Great Depression. Coming to a head in

11745-597: The United States of America to Spain" to seek assistance in the Revolutionary War effort. The first known public usage is an anonymous essay published in the Williamsburg newspaper, The Virginia Gazette , on April 6, 1776. By June 1776, the "United States of America" appeared in the Articles of Confederation and the Declaration of Independence . The Second Continental Congress adopted

11880-601: The United States, slavery was abolished nationally . By 1900, the country had established itself as a great power , a status solidified after its involvement in World War I . After Japan 's attack on Pearl Harbor in December 1941, the U.S. entered World War II . Its aftermath left the U.S. and the Soviet Union as the world's two superpowers and led to the Cold War , during which both countries struggled for ideological dominance and international influence . Following

12015-541: The United States, despite the usage of "the Americas " as the totality of North and South America. "The States" is an established colloquial shortening of the name, used particularly from abroad; "stateside" is the corresponding adjective or adverb. The first inhabitants of North America migrated from Siberia across the Bering land bridge about 12,000 years ago; the Clovis culture , which appeared around 11,000 BC,

12150-624: The United States, except Iran , North Korea , and Bhutan . Though Taiwan does not have formal diplomatic relations with the U.S., it maintains close unofficial relations. The United States regularly supplies Taiwan with military equipment to deter potential Chinese aggression. Its geopolitical attention also turned to the Indo-Pacific when the United States joined the Quadrilateral Security Dialogue with Australia, India, and Japan. The United States has

12285-509: The United States. The American prison system is largely heterogenous, with thousands of relatively independent systems operating across federal, state, local, and tribal levels. In 2023, "these systems [held] almost 2 million people in 1,566 state prisons, 98 federal prisons, 3,116 local jails, 1,323 juvenile correctional facilities, 181 immigration detention facilities, and 80 Indian country jails, as well as in military prisons , civil commitment centers, state psychiatric hospitals, and prisons in

12420-467: The adoption of standardized syllables called "stems" that relate new chemical entities to existing drug families. Stems may be prefixes , suffixes , or interfixes in the nonproprietary name. Each stem can emphasize a specific chemical structure type, a pharmacologic property, or a combination of these attributes. The recommended list of USAN stems is updated regularly to keep pace to accommodate drugs with new chemical and pharmacologic properties. As

12555-485: The advent of increased cell-specific targeting and subcellular trafficking control. Methods for non-viral gene therapy include the injection of naked DNA, electroporation , the gene gun , sonoporation , magnetofection , the use of oligonucleotides , lipoplexes, dendrimers, and inorganic nanoparticles. These therapeutics can be administered directly or through scaffold enrichment . More recent approaches, such as those performed by companies such as Ligandal , offer

12690-410: The brand name Tecelra, is an autologous T cell immunotherapy used for the treatment of synovial sarcoma . It is a T cell receptor (TCR) gene therapy. It is the first FDA-approved engineered cell therapy for a solid tumor. It uses a self-inactivating lentiviral vector to express a T-cell receptor specific for MAGE-A4, a melanoma-associated antigen. Gene therapy approaches to replace a faulty gene with

12825-457: The contiguous United States are in the State of California, about 84 miles (135 km) apart. At an elevation of 20,310 feet (6,190.5 m), Alaska's Denali is the highest peak in the country and continent. Active volcanoes are common throughout Alaska's Alexander and Aleutian Islands , and Hawaii consists of volcanic islands. The supervolcano underlying Yellowstone National Park in

12960-556: The country's GDP. The U.S. has 42% of the world's nuclear weapons —the second-largest share after Russia. The United States has the third-largest combined armed forces in the world, behind the Chinese People's Liberation Army and Indian Armed Forces . The military operates about 800 bases and facilities abroad, and maintains deployments greater than 100 active duty personnel in 25 foreign countries. State defense forces (SDFs) are military units that operate under

13095-469: The country's territory would expand with the admission of new states , rather than the expansion of existing states. The U.S. Constitution was drafted at the 1787 Constitutional Convention to overcome the limitations of the Articles. It went into effect in 1789, creating a federal republic governed by three separate branches that together ensured a system of checks and balances . George Washington

13230-713: The development of self-governance, and the First Great Awakening , a series of Christian revivals , fueled colonial interest in religious liberty . For a century, the American colonists had been providing their own troops and materiel in conflicts with indigenous peoples allied with Britain's colonial rivals , especially France, and the Americans had begun to develop a sense of self-defense and self-reliance separate from Britain. The French and Indian War (1754–1763) took on new significance for all North American colonists after Parliament under William Pitt

13365-580: The environment for labor unions to begin to flourish . This period eventually ended with the advent of the Progressive Era , which was characterized by significant reforms. Pro-American elements in Hawaii overthrew the Hawaiian monarchy ; the islands were annexed in 1898. That same year, Puerto Rico , the Philippines , and Guam were ceded to the U.S. by Spain after the latter's defeat in

13500-541: The federal government often applied policies of Indian removal or assimilation . The Trail of Tears (1830–1850) was a U.S. government policy that forcibly removed and displaced most Native Americans living east of the Mississippi River to lands far to the west. These and earlier organized displacements prompted a long series of American Indian Wars west of the Mississippi. The Republic of Texas

13635-526: The field. The first commercial gene therapy, Gendicine , was approved in China in 2003, for the treatment of certain cancers. In 2011, Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease , including critical limb ischemia . In 2012, alipogene tiparvovec , a treatment for a rare inherited disorder , lipoprotein lipase deficiency , became

13770-961: The first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I . In 2003, Gendicine became the first gene therapy to receive regulatory approval. Since that time, further gene therapy drugs were approved, such as alipogene tiparvovec (2012), Strimvelis (2016), tisagenlecleucel (2017), voretigene neparvovec (2017), patisiran (2018), onasemnogene abeparvovec (2019), idecabtagene vicleucel (2021), nadofaragene firadenovec , valoctocogene roxaparvovec and etranacogene dezaparvovec (all 2022). Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo , respectively. AAVs are characterized by stabilizing

13905-606: The first nuclear weapons and used them against the Japanese cities of Hiroshima and Nagasaki in August 1945, ending the war. The United States was one of the " Four Policemen " who met to plan the post-war world , alongside the United Kingdom , Soviet Union , and China . The U.S. emerged relatively unscathed from the war, with even greater economic power and international political influence . After World War II,

14040-743: The first treatment to be approved for clinical use in either the European Union or the United States after its endorsement by the European Commission . Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered – replacing or disrupting defective genes. Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis , haemophilia, muscular dystrophy , thalassemia , and sickle cell anemia . alipogene tiparvovec treats one such disease, caused by

14175-506: The host cell's nuclear genome at a low frequency and likely mediated by the DNA-modifying enzymes of the host cell. Animal models suggest that integration of AAV genetic material into the host cell's nuclear genome may cause hepatocellular carcinoma , a form of liver cancer . Several AAV investigational agents have been explored in treatment of wet age related macular degeneration by both intravitreal and subretinal approaches as

14310-441: The host cell, tricking the host's cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the nuclear genome of the host cell. Scientists exploit this by substituting part of a virus's genetic material with therapeutic DNA or RNA. Like the genetic material (DNA or RNA) in viruses, therapeutic genetic material can be designed to simply serve as

14445-608: The individual patient only, and are not inherited by offspring . Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid ) is used to treat disease. Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies , haemophilia , thalassaemia , and cystic fibrosis . Such single gene disorders are good candidates for somatic cell therapy. The complete correction of

14580-463: The integration of Army National Guard units and personnel into the U.S. Army and (since 1947) the U.S. Air Force. There are about 18,000 U.S. police agencies from local to national level in the United States. Law in the United States is mainly enforced by local police departments and sheriff departments in their municipal or county jurisdictions. The state police departments have authority in their respective state , and federal agencies such as

14715-482: The military draft (leading to the end of conscription in 1973) and wide opposition to U.S. intervention in Vietnam (with the U.S. totally withdrawing in 1975). A societal shift in the roles of women was significantly responsible for the large increase in female paid labor participation during the 1970s, and by 1985 the majority of American women aged 16 and older were employed. The late 1980s and early 1990s saw

14850-612: The most attractive to the population are the most vulnerable. The U.S. is one of 17 megadiverse countries containing large numbers of endemic species : about 17,000 species of vascular plants occur in the contiguous United States and Alaska, and over 1,800 species of flowering plants are found in Hawaii, few of which occur on the mainland. The United States is home to 428 mammal species, 784 birds, 311 reptiles, 295 amphibians , and around 91,000 insect species. There are 63 national parks , and hundreds of other federally managed parks, forests, and wilderness areas , managed by

14985-662: The most violent, the California genocide of thousands of Native inhabitants, lasted into the early 1870s, just as additional western territories and states were created. During the colonial period, slavery had been legal in the American colonies , though the practice began to be significantly questioned during the American Revolution. States in the North enacted abolition laws , though support for slavery strengthened in Southern states , as inventions such as

15120-1037: The non-viral gene delivery problem. Non-viral techniques offer the possibility of repeat dosing and greater tailorability of genetic payloads, which in the future will be more likely to take over viral-based delivery systems. Companies such as Editas Medicine , Intellia Therapeutics , CRISPR Therapeutics , Casebia , Cellectis , Precision Biosciences , bluebird bio , Excision BioTherapeutics , and Sangamo have developed non-viral gene editing techniques, however frequently still use viruses for delivering gene insertion material following genomic cleavage by guided nucleases . These companies focus on gene editing, and still face major delivery hurdles. BioNTech , Moderna Therapeutics and CureVac focus on delivery of mRNA payloads, which are necessarily non-viral delivery problems. Alnylam , Dicerna Pharmaceuticals , and Ionis Pharmaceuticals focus on delivery of siRNA (antisense oligonucleotides) for gene suppression, which also necessitate non-viral delivery systems. In academic contexts,

15255-660: The north and Mexico to the south, with the states of Alaska to the northwest and the archipelagic Hawaii in the Pacific Ocean . The United States also asserts sovereignty over five major island territories and various uninhabited islands . The country has the world's third-largest land area , largest exclusive economic zone , and third-largest population , exceeding 334 million. Its three largest metropolitan areas are New York , Los Angeles , and Chicago , and its three most populous states are California , Texas , and Florida . Paleo-Indians migrated across

15390-408: The policy of redlining later adopted by the federal Home Owners' Loan Corporation . An explosion of technological advancement accompanied by the exploitation of cheap immigrant labor led to rapid economic expansion during the late 19th and early 20th centuries , allowing the United States to outpace the economies of England, France, and Germany combined. This fostered the amassing of power by

15525-434: The possibility of creating cell-specific targeting technologies for a variety of gene therapy modalities, including RNA, DNA and gene editing tools such as CRISPR. Other companies, such as Arbutus Biopharma and Arcturus Therapeutics , offer non-viral, non-cell-targeted approaches that mainly exhibit liver trophism. In more recent years, startups such as Sixfold Bio , GenEdit , and Spotlight Therapeutics have begun to solve

15660-574: The primary colonial grievances was a denial of their rights as Englishmen , particularly the right to representation in the British government that taxed them . To demonstrate their dissatisfaction and resolve, the First Continental Congress met in 1774 and passed the Continental Association , a colonial boycott of British goods that proved effective. The British attempt to then disarm the colonists resulted in

15795-545: The public domain. This distinguishes them from the trademarked names that have been registered for private use. Assignment of a USAN takes into account practical considerations, such as the existence of trademarks , international harmonization of drug nomenclature, the development of new classes of drugs, and the fact that the intended uses of substances for which names are being selected may change. USANs assigned today reflect both present nomenclature practices and older methods used to name drug entities. Early drug nomenclature

15930-515: The rights of African Americans . National infrastructure, including transcontinental telegraph and railroads , spurred growth in the American frontier . From 1865 through 1917 an unprecedented stream of immigrants arrived in the United States, including 24.4 million from Europe. Most came through the port of New York City , and New York City and other large cities on the East Coast became home to large Jewish , Irish , and Italian populations, while many Germans and Central Europeans moved to

16065-614: The rocky Great Basin and Chihuahua , Sonoran , and Mojave deserts. In the northwest corner of Arizona , carved by the Colorado River over millions of years, is the Grand Canyon , a steep-sided canyon and popular tourist destination known for its overwhelming visual size and intricate, colorful landscape. The Sierra Nevada and Cascade mountain ranges run close to the Pacific coast . The lowest and highest points in

16200-515: The same year, the FDA announced that it had jurisdiction over approving "gene therapy" without defining the term. The FDA added a very broad definition in 1993 of any treatment that would 'modify or manipulate the expression of genetic material or to alter the biological properties of living cells'. In 2018 this was narrowed to 'products that mediate their effects by transcription or translation of transferred genetic material or by specifically altering host (human) genetic sequences'. Writing in 2018, in

16335-573: The six service branches, which are made up of the U.S. Army , Marine Corps , Navy , Air Force , and Space Force . The Coast Guard is administered by the Department of Homeland Security in peacetime and can be transferred to the Department of the Navy in wartime. The United States spent $ 916 billion on its military in 2023, which is by far the largest amount of any country , making up 37% of global military spending and accounting for 3.4% of

16470-545: The sole authority of a state government. SDFs are authorized by state and federal law but are under the command of the state's governor . They are distinct from the state's National Guard units in that they cannot become federalized entities. A state's National Guard personnel, however, may be federalized under the National Defense Act Amendments of 1933 , which created the Guard and provides for

16605-543: The states are also represented by local elected governments , which are administrative divisions of the states. States are subdivided into counties or county equivalents , and further divided into municipalities . The District of Columbia is a federal district containing the U.S. capital, Washington, D.C. . The federal district is an administrative division of the federal government. Federally recognized tribes govern 326 Indian reservations . The United States has an established structure of foreign relations, and it has

16740-510: The structure and responsibilities of the national federal government and its relationship with the individual states. The U.S. Constitution is the world's oldest national constitution still in effect (from March 4, 1789). Composed of three branches, all headquartered in Washington, D.C., the federal government is the national government of the United States. It is regulated by a strong system of checks and balances . The three-branch system

16875-530: The third sponsoring organization in 1964, at which point the name of the committee was changed to the USAN Council, and United States Adopted Name became the official term to describe any nonproprietary name negotiated and formally adopted by the Council. In 1967, a liaison representative from the Food and Drug Administration (FDA) was appointed to serve on the USAN Council. The FDA announced in 1984 that it would discontinue adding drug names to its official list and use

17010-475: The various nomenclature committees, and the medical community in general that a global name be established for each new single-entity compound introduced. Assigning a USAN and standardizing names internationally can take anywhere from several months to a few years. Examples of drugs for which the USAN differs from the INN include: Gene therapy Gene therapy is a medical technology that aims to produce

17145-582: The world's fourth-longest river system , runs predominantly north–south through the heart of the country. The flat and fertile prairie of the Great Plains stretches to the west, interrupted by a highland region in the southeast. The Rocky Mountains , west of the Great Plains, extend north to south across the country, peaking at over 14,000 feet (4,300 m) in Colorado . Farther west are

17280-583: The world's second-largest diplomatic corps as of 2024 . It is a permanent member of the United Nations Security Council , and home to the United Nations headquarters . The United States is a member of the G7 , G20 , and OECD intergovernmental organizations. Almost all countries have embassies and many have consulates (official representatives) in the country. Likewise, nearly all countries host formal diplomatic missions with

17415-444: The world's oldest surviving federation, and its presidential system of national government has been adopted, in whole or in part, by many newly independent states worldwide following their decolonization . It is a liberal representative democracy "in which majority rule is tempered by minority rights protected by law ". The Constitution of the United States serves as the country's supreme legal document , also establishing

17550-553: The world's tornadoes occur in the country , mainly in Tornado Alley . Overall, the United States receives more high-impact extreme weather incidents than any other country. Extreme weather became more frequent in the U.S. in the 21st century, with three times the number of reported heat waves as in the 1960s. In the American Southwest , droughts became more persistent and more severe. The regions considered as

17685-575: Was annexed in 1845, and the 1846 Oregon Treaty led to U.S. control of the present-day American Northwest . Victory in the Mexican–American War resulted in the 1848 Mexican Cession of California, Nevada, Utah, and much of present-day Colorado and the American Southwest . The California gold rush of 1848–1849 spurred a huge migration of white settlers to the Pacific coast, leading to even more confrontations with Native populations. One of

17820-759: Was adopted on July 4, 1776. The political values of the American Revolution included liberty , inalienable individual rights ; and the sovereignty of the people ; supporting republicanism and rejecting monarchy , aristocracy , and all hereditary political power; civic virtue ; and vilification of political corruption . The Founding Fathers of the United States , who included Washington, Jefferson, John Adams , Benjamin Franklin , Alexander Hamilton , John Jay , James Madison , Thomas Paine , and many others, were inspired by Greco-Roman , Renaissance , and Enlightenment philosophies and ideas. The Articles of Confederation were ratified in 1781 and established

17955-553: Was based on the chemical structure . As newer drugs became chemically more complex and numerous, nonproprietary names based on chemistry became long and difficult to spell, pronounce, or remember. Additionally, chemically derived names provided little useful information to non-chemist health practitioners. Considering the needs of health professionals led to a system in which USANs reflect relationships between new entities and older drugs, and avoid names that might suggest non-existent relationships. Current nomenclature practices involve

18090-583: Was elected the country's first president under the Constitution, and the Bill of Rights was adopted in 1791 to allay skeptics' concerns about the power of the more centralized government. His resignation as commander-in-chief after the Revolutionary War and his later refusal to run for a third term as the country's first president established a precedent for the supremacy of civil authority in

18225-433: Was performed by geneticist Martin Cline of the University of California, Los Angeles in California , United States on 10 July 1980. Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified. After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as

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