March 1, 2016 at 7:00 pm

Chemistry Colloquium | Using Medicinal Chemistry to Improve Drug-like Properties of Therapeutic Oligonucleotides, March 21

Punit Seth

Punit Seth

Ohio University’s Chemistry and Biochemistry Colloquium Series presents Dr. Punit Seth on “Using Medicinal Chemistry to Improve the Drug-like Properties of Therapeutic Oligonucleotides” on Monday, March 21, at 4:35 p.m. in Clippinger Laboratories room 194.

Seth currently heads the medicinal chemistry group at Ionis Pharmaceuticals. He is co-inventor of Ionis’ Gen 2.5 platform which employs high affinity nucleoside modifications to enhance potency of antisense oligonucleotides (ASOs) in the liver and in extra-hepatic tissues. Seth is also co-inventor of Inos’ LICA (ligand conjugated antisense oligonucleotides) platform which enhances ASO potency by targeted delivery to cells and tissues of interest. Dr. Seth has extensive experience with using medicinal chemistry strategies to modulate the activity, pharmacokinetics and toxicological properties of ASOs. Dr. Seth is listed as co-author on over 65 peer-reviewed publications and as co-inventor on over 70 issued US patents and international patent applications. He serves on the Scientific Advisory Council of the Oligonucleotide Therapeutic Society (OTS) and has a Ph.D in organic chemistry from The Ohio State University under the tutelage of Dr. Stephen C. Bergmeier.

Abstract: Antisense oligonucleotides (ASOs) bind to their cognate mRNA by Watson-Crick base-pairing and modulate its intermediary metabolism to produce a pharmacological effect. Unmodified oligonucleotides are highly polar, poly-anionic macromolecules which have poor drug-like properties. To address these limitations, medicinal chemists have developed chemical modification and conjugation strategies to improve the RNA-binding affinity, metabolic stability and pharmacokinetic properties of therapeutic oligonucleotides. We have used structure based-design to prepare nucleic acid analogs which enhance the drug-like properties of therapeutic oligonucleotides. Recent developments which improve potency and therapeutic efficacy of ASO drugs in animal models will be presented.

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