Kaiyue Ma

I am doing my PhD training in the Lek Lab at Yale University (2018-present). I am interested at improving diagnostics and developing treatments for rare muscle diseases, especially the muscular dystrophies caused by mutations in the components of the Dystrophin Glycoprotein Complex (DGC).

I led a project examining the functional consequences of all possible small-size variants of alpha-dystroglycanopathy related genes in a high-throughput manner. In this project, I developed a simple, cost-effective, and adaptable workflow for high-throughput functional screening of variants, which was named Saturation mutagenesis-reinforced Functional assays (SMuRF). We have applied SMuRF and screened all possible coding SNVs of FKRP and LARGE1. The Lek lab is expanding SMuRF by incorporating different saturation mutagenesis methods and different functional assays and will apply it to more genes.

I conducted a project to develop a personalized gene therapy which employed the CRISPR-activation technology to up-regulate the cortical dystrophin in patients who lack the muscle isoform. I designed and cloned the CRISPRa construct used to make the clinical drug and performed the pre-clinical studies to test it both in cell lines and mouse models. The Investigational New Drug (IND) Application for the clinical trial of this project was approved by FDA (IND, 28497; https://beta.clinicaltrials.gov/study/NCT05514249).

I have also been working on developing novel systemic delivery systems, including engineered AAV serotypes and antibody-based delivery, to increase safety and delivering efficiency to the muscular tissues.