Table of Contents
What are phosphorothioate oligonucleotides?
Phosphorothioate oligonucleotides are indispensable tools for probing nucleic acid structure and function and for the design of antisense therapeutics. Many applications involving phosphorothioates require site- and stereospecific substitution of individual pro-RP or pro-SP nonbridging oxygens.
How do you make phosphorothioate?
A phosphorothioate bond is produced by using Beaucage reagent to add a sulfer to the phosphate. Once either the sulfer or the oxygen has been attached to the phosphate, the bond is stabilized and will not be affected by the subsequent cycles of chemistry.
What is a PS Aso?
ASO therapeutics are chemically modified and include phosphorothioate (PS) backbone modifications and different ribose and base modifications to improve pharmacological properties. Modified PS ASOs display better binding affinity to the target RNAs and increased binding to proteins.
What is PS DNA?
Phosphorothioate deoxyribonucleotides (PS-DNA) are among the most widely used antisense inhibitors. PS-DNA exhibits desirable properties such as enhanced nuclease resistance, improved bioavailability, and the ability to induce RNase H mediated degradation of target RNA.
What is a Gapmer antisense oligonucleotides?
From Wikipedia, the free encyclopedia. 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.
Are ASOs DNA or RNA?
ASOs are short DNA/RNA oligos which are heavily modified to increase their stability in biological fluids and retain the properties of creating RNA-RNA and DNA-RNA duplexes that knock-down or correct genetic expression.
What is LNA Gapmer?
Antisense LNA GapmeRs are powerful tools for protein, mRNA and lncRNA loss-of-function studies. These single-stranded, antisense oligonucleotides (ASOs) catalyze RNase H-dependent degradation of complementary RNA targets. The central DNA “gap” activates RNase H cleavage of the target RNA upon binding.
Are antisense oligonucleotides DNA?
Abstract. Antisense oligonucleotides (AS ONs) are synthetic DNA oligomers that hybridize to a target RNA in a sequence-specific manner. They have successfully been employed to inhibit gene expression, modulate splicing of a precursor messenger RNA, or inactivate microRNAs.
Which is antisense technology?
Antisense DNA technology is a method to inhibit or downregulate the production of a target protein by using antisense DNA or RNA molecules. An antisense sequence is a DNA or RNA that is perfectly complementary to the target nucleotide sequence present in the cell.
Are antisense oligonucleotides DNA or RNA?
Antisense Oligonucleotide. ASOs are single-stranded, highly-modified, synthetic RNA (or DNA) sequences, designed to selectively bind via complementary base-pairing to RNA which encodes the gene of interest, and have been tested in a number of disorders [29].
How is the phosphorothioate bond used in DNA?
Phosphorothioate Bond The phosphorothioate (PS) bond substitutes a sulfur atom for a non-bridging oxygen in the phosphate backbone of an oligo. This modification renders the internucleotide linkage resistant to nuclease degradation.
How are phosphorothioate modified oligonucleotides interact with proteins?
ASO therapeutics are chemically modified and include phosphorothioate (PS) backbone modifications and different ribose and base modifications to improve pharmacological properties. Modified PS ASOs display better binding affinity to the target RNAs and increased binding to proteins.
How does phosphorothioate increase resistance to ASOS?
Phosphorothioate (PS) modifications confer increased resistance to the nucleases that degrade ASOs thereby extending their tissue elimination half-lives (for review, see ( 8, 13 )).
Which is substituted for oxygen in a phosphorothioate bond?
Phosphorothioate Bond. The phosphorothioate (PS) bond substitutes a sulfur atom for a non-bridging oxygen in the phosphate backbone of an oligo.