CMTA Awards Gladstone Institutes and UCSF $653,000 Grant for Gene Editing Project

Drs. Conklin & Judge

Drs. Bruce Conklin and Luke Judge of the Gladstone Institutes and UCSF Departments of Medicine and Pediatrics will use a $653,000 grant from the CMTA in 2020 to develop the gene-editing technique known as CRISPR for application to CMT2A, 2E and 2F.

Gene editing is a group of technologies that give researchers and scientists the ability to modify DNA. Genetic material can be added, removed or altered at certain locations in the genome, much like cutting and pasting information in a Word document. Methods to modify DNA in the genome have been around for more than 30 years, but CRISPR technology has brought major improvements in the speed, cost, accuracy and efficiency of gene editing.

Drs. Conklin and Judge, leaders in genome editing, and their team (www.ConklinLab.org) have already made substantial progress in testing CRISPR in stem cell models of CMT2A and CMT2E. The San Francisco Bay area is at the forefront of technology development in the field: In 2012, Dr. Jennifer Doudna and her team at Berkeley discovered how CRISPR could be used for DNA editing. Dr. Doudna now directs the Innovative Genomics Institute (IGI), where Dr. Conklin serves as deputy director (https://innovativegenomics.org/). The newly funded project will focus on developing the pre-clinical tools and preliminary data needed to take the next steps for eventually testing CRISPR therapies in human clinical trials.

Cutting-Edge Gene Editing

The history of gene editing technologies shows the remarkable progress in this field and the critical role that basic science research plays in the development of research tools and potential disease treatments. Editing the genomes of rodents and other organisms that scientists commonly study has brought forward numerous discoveries about how the genome is connected to physical traits like eye color and diseases like CMT.

CRISPR can make deletions in the genome and/or be engineered to insert new DNA sequences. The CRISPR system was adapted from a naturally occurring gene editing systems in bacteria. The bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to “remember” the viruses so that if they attack again, the bacteria can target their DNA. Remarkably, this bacterial defense system works in human cells to edit DNA and perhaps treat genetic diseases.

While many leading scientists believe that the use of CRISPR in clinical trials is still years away, the studies have the potential to advance this technology for CMT and set a new standard for therapeutic engineering for motor neuron disease that can be extended to other neurological diseases.