Bench to Bedside: Chemistry of Health Care

Oligonucleotide Therapeutics: From Base Pairs to Bedsides (#8)

Oligonucleotides can function as drugs through interactions with RNA, DNA, or proteins and they provide an alternate attractive strategy to small molecules and antibodies based drug discovery. Over the past several years, RNAi therapeutics based on short interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), microRNAs (miRNAs), antagomirs (antimirs), and splice-altering oligonucleotides have been developed to target RNA. Protein-oligonucleotide interactions are the focus of the technology based on aptamers, microRNA mimics and immunostimulatory oligonucleotides. Long non-coding RNAs (lncRNAs) and long synthetic mRNAs are also emerging as therapeutic strategies. Three oligonucleotide compounds have been approved by FDA. There are nearly 100 oligonucleotide drugs in various stages of clinical trials around the world and many of them focus on “non-druggable” disease targets (by conventional therapies) and orphan diseases. As oligonucleotides are not drug-like in the traditional sense and, therefore, a major challenge has been to modify these molecules to impart favorable "drug-like" properties without compromising specificity. This symposium will cover aspects related to oligonucleotide therapeutics, including a) fundamental mechanisms, b) chemical modifications of oligonucleotides, c) structural biology of the enzyme-oligonucleotide complexes, d) methods of drug delivery based on nanoparticles, polymers, and oligonucleotide conjugates, and e) clinical development and recent clinical successes, bringing leaders from academia and industry to discuss the above topics.

Last update: Dec 28, 2015