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19th Ave New York, NY 95822, USA

Qian, Ziqing “Leo”

Ziqing "Leo" Qian

Entrada Therapeutics

Talk Session: SESSION 5: PEPTIDE AND PROTEIN CONJUGATES
Date: Monday, June 13, 2022
Talk Time: 11:35 am - 11:55 am
Talk Title: Development of Endosomal Escape Vehicles to Enhance the Intracellular

Ziqing, "Leo," Qian, Ph.D., is co-founder and Vice President, Discovery Research at Entrada Therapeutics, a Boston-based biotechnology company dedicated to transforming the treatment of devastating diseases using intracellular therapeutics. Dr. Qian co-invented Entrada’s Endosomal Escape Vehicle, EEV™ platform, which is applied to the design and development of intracellular delivery of otherwise impermeable biological cargos, including oligonucleotides, proteins, and peptides. Leo obtained his Ph.D. in Organic Chemistry from The Ohio State University. He has co-authored over thirty peer-reviewed publications and two book chapters, as well as co-inventor on over ten patents.

Biological therapeutics exhibit high target specificity and potency but are limited in their ability to reach intracellular targets of interest. These limitations often necessitate high therapeutic doses and can be associated with less-than-optimal therapeutic activity.

One promising solution for the intracellular delivery of biologics is through the use of cell-penetrating peptides, CPPs. However, canonical CPPs are limited by relatively low efficiencies of cellular uptake and endosomal escape, minimal proteolytic stability, and toxicity. To overcome these limitations, we have designed a family of proprietary cyclic CPPs that form the core of our Endosomal Escape Vehicle, EEV™, technology, which is capable of delivering covalently conjugated cargo across all tissue types.

To demonstrate the utility of our platform, we employed our EEV technology for the delivery of splice-modulating oligonucleotides and evaluated the EEV-oligonucleotide conjugates in preclinical models of Duchenne muscular dystrophy, DMD. EEV-oligonucleotide conjugates demonstrated durable exon skipping and broad dystrophin protein expression in target tissues including skeletal and cardiac muscles.

These results suggest the significant therapeutic potential of our EEV-oligonucleotides for neuromuscular diseases, as well as the broader application of our EEV platform for the delivery of intracellular therapeutics.

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