Development of Coagulation Factor VIII Transgenes That Confer Greater Potency to Gene Therapies for Hemophilia A Through Ancestral Sequence Reconstruction
Highlights from the ASGCT 23rd Annual Meeting

Development of Coagulation Factor VIII Transgenes That Confer Greater Potency to Gene Therapies for Hemophilia A Through Ancestral Sequence Reconstruction

Christopher Coyle1, Jasmine Anickat2, Alex Condra2, Luke Blackmon2, Philip M. Zakas3, H. Trent Spencer4, Eric A. Gaucher5, Christopher B. Doering4

1Graduate Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, GA

2Department of Biology, Emory University, Atlanta, GA

3Gene Therapy, Rare Blood Disorders, Sanofi, U.S., Waltham, MA

4Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA

5Department of Biology, Georgia State University, Atlanta, GA

Key Data Points

In order to increase expression and durability of factor proteins, researchers at Emory University, Georgia State University, and Sanofi are testing alternate DNA sequences for FVIII and FIX based on evolutionary variants of these coagulation factors. This process, known as ancestral sequence reconstruction, was used to identify nodes of interest (red circles in the diagram on the left) from the phylogenetic tree for FVIII and these sequences (table on the right) are being tested for in vitro expression.

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