Identification of coagulation factor IX variants with enhanced activity through ancestral sequence reconstruction.

ABSTRACT: Orthologous proteins contain sequence disparity guided by natural selection. In certain cases, species-specific protein functionality predicts pharmacological enhancement, such as greater specific activity or stability. However, immunological barriers generally preclude use of nonhuman proteins as therapeutics, and difficulty exists in the identification of individual sequence determinants among the overall sequence disparity. Ancestral sequence reconstruction (ASR) represents a platform for the prediction and resurrection of ancient gene and protein sequences. Recently, we demonstrated that ASR can be used as a platform to facilitate the identification of therapeutic protein variants with enhanced properties. Specifically, we identified coagulation factor VIII (FVIII) variants with improv

SUBMITTER: Knight KA 

PROVIDER: S-EPMC8525220 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature