Developing Safer CRISPR Genetic Therapies

Benjamin Kleinstiver, PhD
Benjamin Kleinstiver, PhD
MGH Research Scholar 2023-2028
Assistant Investigator, Center for Genomic Medicine
Assistant Professor of Pathology, Harvard Medical School

CRISPR (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats. It is a technology based on naturally occurring genome editing systems found in bacteria that scientists use to selectively modify the DNA of living organisms.

Most human diseases are caused by erroneous DNA alterations in an individual's genome. Approaches to modify the genomes of patients have recently shown promise to correct various genetic mutations, with CRISPR-derived technologies leading the way as a new class of genomic medicines.

However, naturally occurring CRISPR enzymes, which originally evolved as part of bacterial immune systems, may not be optimal tools for safe and effective genetic therapies.

CRISPR enzymes are often unable to install the desired corrective genetic edit, they can lead to unwanted deleterious side effects, and can lack the versatility necessary to treat diseases cause by a range of mutations. My laboratory  strives to meet these unmet needs and close these knowledge gaps.

To overcome these challenges, we are pioneering the use of molecular engineering methods to alter and improve the properties of genome editing technologies.

We endeavor to engineer highly safe, precise and effective CRISPR enzymes with expanded capabilities that enable pre-clinical studies to treat several human diseases, including those for which there are no effective cures, to alleviate the suffering of patients.