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Gapmer
Gapmers are short DNA antisense oligonucleotide structures with RNA-like segments on both sides of the sequence. These linear pieces of genetic information are designed to hybridize to a target piece of RNA and silence the gene through the induction of RNase H cleavage. Binding of the gapmer to the target has a higher affinity due to the modified RNA flanking regions, as well as resistance to degradation by nucleases.QIAGEN. (2017). Antisense LNA GapmeRs Handbook: LNA-optimized oligonucleotides for strand-specific knockdown of mRNA and IncRNA. Germantown, MD: Author Gapmers are currently being developed as therapeutics for a variety of cancers, viruses, and other chronic genetic disorders. Chemical Structure Gapmers are composed of short DNA strands flanked by strands of RNA mimics. The mimics are typically composed of locked nucleic acids (LNA), 2'-OMe, or 2'-F modified bases. LNA sequences are RNA analogues "locked" into an ideal Watson-Crick base pairing conformation. Gapmers ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oligonucleotide
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase chemical synthesis, these small fragments of nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence, and so are vital for artificial gene synthesis, polymerase chain reaction (PCR), DNA sequencing, molecular cloning and as Fluorescence in situ hybridization, molecular probes. In nature, oligonucleotides are usually found as small RNA molecules that function in the regulation of gene expression (e.g. microRNA), or are degradation intermediates derived from the breakdown of larger nucleic acid molecules. Oligonucleotides are characterized by the Nucleic acid sequence, sequence of nucleotide residues that make up the entire molecule. The length of the oligonucleotide is usually denoted by "Monomer, -m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mipomersen
Mipomersen (International Nonproprietary Name, 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 unexp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sense (molecular Biology)
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, sense may have slightly different meanings. For example, the negative-sense strand of DNA is equivalent to the template strand, whereas the positive-sense strand is the non-template strand whose nucleotide sequence is equivalent to the sequence of the mRNA transcript. DNA sense Because of the complementary nature of base-pairing between nucleic acid polymers, a double-stranded DNA molecule will be composed of two strands with sequences that are reverse complements of each other. To help molecular biologists specifically identify each strand individually, the two strands are usually differentiated as the "sense" strand and the "antisense" strand. An individual strand of DNA is referred to as positive-sense (also positive (+) or simply se ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oligonucleotide Synthesis
Oligonucleotide synthesis is the chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure (sequence). The technique is extremely useful in current laboratory practice because it provides a rapid and inexpensive access to custom-made oligonucleotides of the desired sequence. Whereas enzymes synthesize DNA and RNA only in a 5' to 3' direction, chemical oligonucleotide synthesis does not have this limitation, although it is most often carried out in the opposite, 3' to 5' direction. Currently, the process is implemented as solid-phase synthesis using phosphoramidite method and phosphoramidite building blocks derived from protected 2'-deoxynucleosides ( dA, dC, dG, and T), ribonucleosides ( A, C, G, and U), or chemically modified nucleosides, e.g. LNA or BNA. To obtain the desired oligonucleotide, the building blocks are sequentially coupled to the growing oligonucleotide chain in the order required by the sequence of the product (s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antisense Therapy
Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-mRNA, direct steric blockage, and exon content modulation through Splicing (genetics), splicing site binding on pre-mRNA. Several ASOs have been approved in the United States, the European Union, and elsewhere. Nomenclature The common stem for antisense oligonucleotides drugs is -rsen. The substem -virsen designates antiviral antisense oligonucleotides. Antisense Oligonucleotide Development Developments in ASO modification are separated into three generations. Generation one is called backbone-modified and focuses on the phosphodiester group of the nucleotide. This impacts inter-nucleotide binding. These modifications led to better distribution, reduced urinary excretion, and prolonged residence time of the ASOs in the cell. Some exam ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transthyretin
Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol''. The liver secretes TTR into the blood, and the choroid plexus secretes TTR into the cerebrospinal fluid. TTR was originally called prealbumin (or thyroxine-binding prealbumin) because it migrated faster than albumin on electrophoresis gels. Prealbumin was felt to be a misleading name, it is not a synthetic precursor of albumin. The alternative name TTR was proposed by DeWitt Goodman in 1981. Human transthyretrin protein is encoded by the ''TTR'' gene, which is located on the long arm of chromosome 18, in cytogenetic band 18q12.1. Binding affinities It functions in concert with two other thyroid hormone-binding proteins in the serum: In cerebrospinal fluid TTR is the primary carrier of T4. TTR also acts as a carrier of retinol ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inotersen
Inotersen, sold under the brand name Tegsedi, is a 2'-O-(2-methoxyethyl) (2'-MOE) antisense oligonucleotide medication used for the treatment of nerve damage in adults with hereditary transthyretin-mediated amyloidosis. The sequence is TCTTG GTTACATGAA ATCCC, where C is methylated C, and the first and third section (bases 1-5 and 16–20, separated from the middle section by spaces) are MOE-modified. The most common side effects are injection site reactions (redness, swelling, bleeding, pain, rash, and itching at the injection site), nausea, headache, tiredness, low platelet counts, and fever. Inotersen can cause serious side effects, including low platelet counts and kidney inflammation. Because of these serious side effects, Inotersen is available in the United States only through a restricted program called the Tegsedi Risk Evaluation and Mitigation (REMS) Program. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. History Inoters ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Familial Amyloid Polyneuropathy
Familial amyloid polyneuropathy, also called hereditary transthyretin amyloidosis (hATTR), or Corino de Andrade's disease, is an autosomal dominant neurodegenerative disease. It is a form of amyloidosis, and was first identified and described by Portuguese neurologist Mário Corino da Costa Andrade, in 1952. FAP is distinct from senile systemic amyloidosis (SSA), which is not inherited, and which was determined to be the primary cause of death for 70% of supercentenarians who have been autopsied. FAP can be ameliorated by liver transplantation. Presentation Usually manifesting itself between 20 and 40 years of age, it is characterized by pain, paresthesia, muscular weakness and autonomic dysfunction. In its terminal state, the kidneys and the heart are affected. FAP is characterized by the systemic deposition of amyloidogenic variants of the transthyretin protein, especially in the peripheral nervous system, causing a progressive sensory and motor polyneuropathy. Cause ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Low-density Lipoprotein
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 Cell (biology), cells. LDL has been associated with the progression of atherosclerosis. 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 22–27.5 nanometers in diameter, typically transporting 3,000 to 6,000 fat molecules per part ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apolipoprotein B
Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Its measurement is commonly used to detect the risk of Atherosclerosis, atherosclerotic Coronary artery disease, cardiovascular disease. Isoforms The protein occurs in the blood plasma, plasma in two main isoforms, ApoB48 and ApoB100. The first is synthesized exclusively by the small intestine, the second by the liver. ApoB-100 is the largest of the apoB group of proteins, consisting of 4563 amino acids, including a 27-amino acid signal peptide and a 4536-amino acid mature protein. Both isoforms are coded by ''APOB'' and by a single mRNA transcript larger than 16 kb. ApoB48 is generated when a stop codon (UAA) at residue 2153 is created by RNA editing. There appears to be a ''trans''-acting tissue-specific splicing gene that determines which isoform is ultimately produced. Alternatively, there is some evidence that a ''cis''-acting element several thousand base pair, bp upstream determines which isof ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
