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UID:20250626T134139EDT-7182bIZwXf@132.216.98.100
DTSTAMP:20250626T174139Z
DESCRIPTION:Abstract:\n\n \n\nSynthetic small interfering RNAs (siRNAs) are
  potent inhibitors of gene expression. These molecules are perfect example
 s of biomimetic chemistry as synthetic siRNAs act through the natural RNA 
 interference (RNAi) pathway. To deliver therapeutic siRNAs into human live
 r\, we developed approaches that include chemical modification of the siRN
 As and either lipid nanoparticle (LNP) formulation or multivalent N-acetyl
 galactosamine (GalNAc) conjugation\, making possible intravenous and subcu
 taneous administration\, respectively. The design of chemical modification
 s of siRNAs to enable favorable Argonaute2 (Ago2) recognition as well as b
 oth delivery strategies rely on biomimetics. The LNP approach is based on 
 the endogenous Apo-E ligand /LDL receptor process. Using these strategies 
 five approved RNAi therapeutics have emerged from Alnylam. We have also us
 ed lipid conjugates for CNS delivery of therapeutic siRNAs. \n\nThis prese
 ntation will cover the molecular basis of RNA therapeutics including the c
 hemical modifications and motifs used in each RNA strand to ensure uptake 
 into cells of the targeted tissue\, Ago2 recognition\, silencing efficienc
 y\, metabolic stability\, and safety.\n\n \n\nBio:\n\nDr. Muthiah (Mano) M
 anoharan serves as the Senior Vice President of Drug Innovation\, a Scient
 ific Advisory Board Member\, and a Distinguished Research Scientist at Aln
 ylam Pharmaceuticals\, Cambridge\, Massachusetts. In 2003\, he was the fou
 nding chemist hired at Alnylam as the Head of the Drug Discovery. He and h
 is team pioneered the discovery and development of numerous chemical modif
 ications\, GalNAc conjugation chemistry\, lipid conjugates (the first in v
 ivo demonstration of RNAi in 2004) and Lipid Nanoparticles (LNP) delivery 
 platform that make RNA interference-based human therapeutics possible. Thi
 s work led to the approval of five RNAi therapeutics: ONPATTRO® (patisiran
 \, 2018)\, GIVLAARI® (givosiran\, 2019)\, OXLUMO® (lumasiran\, 2020)\, LEQ
 VIO® (inclisiran\, 2020\, 2021) and AMVUTTRO® (vutrisiran\, 2022).\n\nDr. 
 Manoharan has had a distinguished career as a world-leading chemist in the
  field of oligonucleotide therapeutics. Prior to joining Alnylam\, he work
 ed at Isis (Ionis) Pharmaceuticals from 1990-2003 in the field of antisens
 e oligonucleotides. He is an author of more than 250 publications (nearly 
 65\,300 Google Scholar citations with an h-index of 116 and an i10-index o
 f 436) and over 500 abstracts\, as well as an inventor of over 290 issued 
 U.S. patents.\n\nDr. Manoharan is the winner of the Lifetime Achievement A
 ward of the Oligonucleotide Therapeutics Society (OTS\, 2019)\, the M. L. 
 Wolfrom Award (2007)\, D. Horton Industrial Carbohydrate Chemistry Award (
 2021) from the Carbohydrate Chemistry Division of the American Chemical So
 ciety\, the Chemical Research Society of India (CRSI) 2022 Medal by the Co
 uncil of the Chemical Research Society of India and the National Chemical 
 Laboratory (NCL\, Pune\, India)-K. N. Ganesh award in 2023 . He was electe
 d as a Fellow of the American Chemical Society in 2022. He has been honore
 d with the Professor Ronald Breslow Biomimetic Chemistry National award by
  the American Chemistry for the year 2024.\n\nDr. Manoharan was born in Ma
 durai\, Tamil Nadu\, India and received his B.Sc. and M.Sc. degrees in che
 mistry at the American College\, Madurai\, India. He earned his Ph.D. in c
 hemistry at the University of North Carolina\, Chapel Hill\, (Professor Er
 nest L. Eliel) and learned the field of oligonucleotides at Yale Universit
 y and University of Maryland as a post-doctoral research associate (Profes
 sor John A. Gerlt).\n\n \n\n \n\n \n
DTSTART:20240227T180000Z
DTEND:20240227T193000Z
LOCATION:OM 10
SUMMARY:Chemical Society Seminar: Muthiah Manoharan-Living in the World of 
 Nucleic Acids Therapeutics: Challenges and Opportunities
URL:/chemistry/channels/event/chemical-society-seminar
 -muthiah-manoharan-living-world-nucleic-acids-therapeutics-challenges-and-
 354055
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