Conklin’s team is focused on using CRISPR-related technology to treat incurable genetic diseases. By focusing on human mutations that are highly penetrant, they use patient-specific iPSCs to derive the disease tissue, and model genome surgery, prior to human clinical trials. They use whole-genome sequencing to identify common genetic polymorphisms, which can be used to selectively inactivate the disease allele with CRISPR nucleases. The diseased cell types allow them to decode the cellular signatures of disease and determine if the excision of the disease allele restores cellular functioning.

Genome surgery is a rapidly advancing field that uses state-of-the-art techniques to push the boundaries of cell and molecular biology. This laboratory uses advanced microscopy, tissue engineering, and single-cell genomics to optimize precise editing. They are also developing computational methods to select optimal CRISPR/Cas9 combinations for each disease gene. They aim to produce therapies that are safe and cost effective so they can benefit the maximal number of people. In collaboration with clinical scientists and the Innovative Genomics Institute, they are preparing large animal models and clinical-grade reagents for human clinical trials.