Characterizing Oligonucleotides With Locked Nucleic Acid Chemistry

Antisense oligonucleotide (ASO) technology has accelerated drug discovery in the last few decades with several ASO-based drugs currently approved by FDA and many more being investigated in clinical trials. Chemical modifications to ASOs affect their physical and chemical properties, helping researchers design more efficient and potent ASO-based drugs. This webinar will explore the most recent ASO chemical modification: locked nucleic acid (LNA), which confers high potency. Our expert speakers will provide insights into the critical in vitro and in vivo steps involved in the characterization of an oligonucleotide with LNA chemistry. Antisense oligonucleotides (ASOs) are single-stranded DNA molecules that can alter the expression of targeted genes through a variety of mechanisms of action, providing potential precision therapy for various human diseases. Unmodified ASOs are not stable in the cellular environment, therefore the need for novel chemical designs. The most recent chemical modification is the locked nucleic acid (LNA) which confers high potency to the ASO, while their safety evaluation is ongoing. This webinar will provide insights into the critical steps involved in the characterization of an oligonucleotide with LNA chemistry. Topics include: • Screening cascade to select optimal ASOs for in vivo studies • Investigation of in vivo biodistribution of LNA antisense oligonucleotides in rodents • Building a PK/PD model for the main organs of accumulation and elimination of oligonucleotides Elisabetta De Filippo, PhD Senior Research Scientist She/Her Evotec Elisabetta.defilippo@evotec.com Elisabetta received her PhD focused on the establishment of in vitro screening cascades and assays for small molecule selection and characterization from the University of Bonn. She is currently a Senior Research Scientist at Evotec, where she leads projects into metabolic and renal disease, including early drug discovery projects developing antisense oligonucleotide-based molecules. Annalisa Mercuri, PhD Research Expert She/Her Other: Evotec annalisa.mercuri@evotec.com Annalisa received her PhD in Pharmaceutics from the University of East Anglia, where she investigated the physico-chemical properties of self-emulsifying drug delivery systems. She is currently a research expert at Evotec, where she focuses on DMPK studies in drug discovery projects for small molecules and multimodalities.