Antisense MRNA
Antisense RNA (asRNA), also referred to as antisense transcript, natural antisense transcript (NAT) or antisense oligonucleotide, is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) with which it hybridizes, and thereby blocks its translation into protein. asRNAs (which occur naturally) have been found in both prokaryotes and eukaryotes, and can be classified into short (200 nucleotides) non-coding RNAs (ncRNAs). The primary function of asRNA is regulating gene expression. asRNAs may also be produced synthetically and have found wide spread use as research tools for gene knockdown. They may also have therapeutic applications. Discovery and history in drug development Some of the earliest asRNAs were discovered while investigating functional proteins. An example was micF asRNA. While characterizing the outer membrane porin in ''E.coli'', some of the promoter clones observed were capable of repressing the expression of other membrane porin s ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Intergenic Region
An intergenic region is a stretch of DNA sequences located between genes. Intergenic regions may contain functional elements and junk DNA. ''Inter''genic regions should not be confused with ''intra''genic regions (or introns), which are non-coding regions that are found ''within'' genes, especially within the genes of eukaryotic organisms. Properties and functions Intergenic regions may contain a number of functional DNA sequences such as promoters and regulatory elements, enhancers, spacers, and (in eukaryotes) centromeres. They may also contain origins of replication, scaffold attachment regions, and transposons and viruses. Non-functional DNA elements such as pseudogenes and repetitive DNA, both of which are types of junk DNA, can also be found in intergenic regions—although they may also be located within genes in introns. As all scientific knowledge is ultimately tentative—and in principle subject to revision given better evidence—it is possible s ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Bacteriophage
A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes (e.g. MS2) and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm. Bacteriophages are among the most common and diverse entities in the biosphere. Bacteriophages are ubiquitous viruses, found wherever bacteria exist. It is estimated there are more than 1031 bacteriophages on the planet, more than every other organism on Earth, including bacteria, combined. Viruses are the most abundant biological entity in the water column of the world's oceans, and the second largest component of biom ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; however, plasmids are sometimes present in archaea and eukaryotic organisms. In nature, plasmids often carry genes that benefit the survival of the organism and confer selective advantage such as antibiotic resistance. While chromosomes are large and contain all the essential genetic information for living under normal conditions, plasmids are usually very small and contain only additional genes that may be useful in certain situations or conditions. Artificial plasmids are widely used as vectors in molecular cloning, serving to drive the replication of recombinant DNA sequences within host organisms. In the laboratory, plasmids may be introduced into a cell via transformation. Synthetic plasmids are available for procurement over the inter ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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RNAse H
Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/ DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from bacteria to archaea to eukaryotes. The family is divided into evolutionarily related groups with slightly different substrate preferences, broadly designated ribonuclease H1 and H2. The human genome encodes both H1 and H2. Human ribonuclease H2 is a heterotrimeric complex composed of three subunits, mutations in any of which are among the genetic causes of a rare disease known as Aicardi–Goutières syndrome. A third type, closely related to H2, is found only in a few prokaryotes, whereas H1 and H2 occur in all domains of life. Additionally, RNase H1-like retroviral ribonuclease H domains occur in multidomain reverse transcriptase proteins, which are encoded by retroviruses such as HIV and are required for viral repl ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Very Low-density Lipoprotein
Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lipoprotein, high-density lipoprotein) that enable fats and cholesterol to move within the water-based solution of the bloodstream. VLDL is assembled in the liver from triglycerides, cholesterol, and apolipoproteins. VLDL is converted in the bloodstream to low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL). VLDL particles have a diameter of 30–80 nm. VLDL transports endogenous products, whereas chylomicrons transport exogenous (dietary) products. In the early 2010s both the lipid composition and protein composition of this lipoprotein were characterised in great detail. Function Very-low-density lipoproteins transport endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters. It functions a ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Apolipoprotein B
Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Function Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, Lp(a), IDL, and LDL particles (LDL—commonly known as "bad cholesterol" when in reference to both heart disease and vascular disease in general), which is responsible for carrying fat molecules (lipids), including cholesterol, around the body to all cells within all tissues. While all the functional roles of ApoB within the LDL (and all larger) particles remain somewhat unclear, it is the primary organizing protein (of the entire complex shell enclosing/carrying fat molecules within) component of the particles and is absolutely required for the formation of these particles. What is also clear is that the ApoB on the LDL particle acts as a ligand for LDL receptors in various cells throughout the body (i.e., less formally, ApoB indicates fat carrying particles are ready to enter any cells with ApoB receptors and deliver fat ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Familial Hypercholesterolemia
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL cholesterol), in the blood and early cardiovascular disease. The most common mutations diminish the number of functional LDL receptors in the liver. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH (such as dietary modification and statin tablets). Nevertheless, treatment (including higher statin doses) is usually effective. FH is classified as a type 2 familial dyslipidemia. There are five types of familial dyslipidemia (not including subtypes), and each are classified from both the altered lipid profile and by the genetic abnormality. For example, high LDL (often due to LDL receptor defect) is type 2. Others include defects in chylomicron ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Low-density Lipoprotein Cholesterol
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density naming convention), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries. Overview Lipoproteins transfer lipids (fats) around the body in the extracellular fluid, making fats available to body cells for receptor-mediated endocytosis. Lipoproteins are complex particles composed of multiple proteins, typically 80–100 proteins per particle (organized by a single apolipoprotein B for LDL and the larger particles). A single LDL particle is about 220–275 angstroms in diameter, typically transporting 3,000 to 6,000 fat ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Mipomersen
Mipomersen (INN; trade name Kynamro) is a drug used to treat homozygous familial hypercholesterolemia and is administered by subcutaneous injection. There is a serious risk of liver damage from this drug and it can only be prescribed in the context of a risk management plan. Indications Kynamro is used to treat homozygous familial hypercholesterolemia and is administered by injection. It cannot be freely prescribed; instead every person put on mipomersen is enrolled in a Risk Evaluation and Mitigation Strategies (REMS) program approved by the FDA. Pregnancy and lactation Mipomersen is pregnancy category B; women who are pregnant or intending to become pregnant should only use this drug if needed. It is unknown if it is secreted in human breast milk, but it was found to be secreted in the breast milk of rats. Contraindications The drug is contraindicated in people with moderate to severe liver impairment, active liver diseases, and unexplained high levels of transaminase ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Cytomegalovirus Retinitis
Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, 15-40% of those with AIDS. Signs and symptoms The symptoms of cytomegalovirus retinitis have it usually starting in one eye (and also have the possibility of retinal detachment), presenting as: * Blurred vision * Blind spots * Specks in your vision Cause Cytomegalovirus (a type of herpes virus) is what causes cytomegalovirus retinitis. Other types of herpes viruses include herpes simplex viruses and Epstein-Barr virus. Once an individual is infected with these viruses they stay in the body for life. What triggers the virus to reactivate are the following (though CMV can also be congenital). * Leukemia * AIDS * Immunosuppressive chemotherapy Mechanism Human cytomegalovirus (HCMV or CMV) is a DNA virus in the family ''Herpesviridae'' known for ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Fomivirsen
Fomivirsen (brand name Vitravene) is an antisense antiviral drug that was used in the treatment of cytomegalovirus retinitis (CMV) in immunocompromised patients, including those with AIDS. It was administered via intraocular injection. It was discovered at the NIH and was licensed and initially developed by Isis Pharmaceuticals, which subsequently licensed it to Novartis. It was licensed by the FDA for CMV in Aug 1998, and was the first antisense drug that was approved. Novartis withdrew the marketing authorization in the EU in 2002 and in the US in 2006. The drug was withdrawn because while there was a high unmet need for drugs to treat CMV when the drug was initially discovered and developed due to the CMV arising in people with AIDS, the development of HAART dramatically reduced the number of cases of CMV. It is an antisense oligonucleotide -- a synthetic 21 member oligonucleotide with phosphorothioate linkages (which are resistant to degradation by nucleases) and has ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |