Introducing Favorable Mutations of Polymerase Orthologs in Human DNA Polymerase

Abstract

This paper explores the possibilities of introducing mutations and features from the T4 bacteriophage’s DNA polymerase into human DNA. It first starts off with questions about the effectiveness of polymerase, a key protein in all cells, and looks for ways to improve it. It then discusses the L412M mutation, found in the finger domain of the polymerase. This mutation increases the processivity of the polymerase, an important trait vital to the protein’s efficiency. L412M also affects fidelity, which is the property of the polymerase that measures accuracy. It pushes the accuracy rate much higher and creates less chance for the development of mutations. The paper also discusses CasPlus, which involves the use of T4 polymerase in conjunction with CRISPR, a common gene editing tool, in order to reduce on-target activity and improve accuracy. The addition of the polymerase decreases the chance that larger deletions will occur. It also prevents chromosomes from moving while the editing process occurs. This would mean that if humans can produce polymerases similar to those in bacteriophages, it would be able to accept future edits with less risk, and therefore, reduce one of the risks in somatic gene editing. Finally, the paper moves on to the process of implementation of the features, as well as discussing the ethics of the overall issue. It cautions a stance that is forward-looking, yet concerned with the moral and societal impact of the solution and promoting equality while pushing the treatment.