Chun-Yu Chen, PhD, on Addressing Hemophilia A With CRISPR/Cas9 mRNA LNP Gene Editing

“Our strategy is to correct the mutant FVIII gene in hemophilia patients.”

Currently, patients with Hemophilia A have a number of treatment options that can be effective for some people with the disease. One of the main treatment options is receiving regular infusions of exogenous factor VIII (FVIII), which is the protein that is deficient in patients with the disease because of a mutation in the gene that codes for it. One of the main drawbacks of this treatment option is that it requires patients to undergo regular infusions of the protein, sometimes on a weekly basis.

More recently, FDA-approved adeno-associated virus (AAV) vector-based gene therapy has become available for hemophilia A in the form of BioMarin’s valoctocogene roxaparvovec (val-rox, marketed as Roctavian), a one-time treatment that enables sustained expression of FVIII through the provision of a functional copy of the disease-targeted gene. This approach also carries important limitations, however. For example, patients who have preexisting antibodies to the AAV capsid are ineligible to receive the treatment, and in the event that the treatment’s efficacy weakens over time, it cannot be redosed. As such, significant unmet need remains for the hemophilia A community and research into new treatment options is ongoing.

The lab of Carol Miao, PhD, a principal investigator at Seattle Children’s Research Institute, is currently working on the development of new treatment options for hemophilia A. Notably, Chun-Yu Chen, PhD, a research scientist in the Miao Lab, presented findings from mouse model research on an approach to treating hemophilia A with CRISPR/Cas9 mRNA lipid nanoparticle (LNP) gene editing at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD. At the conference, CGTLive® sat down with Chen to learn more about the potential advantages of the approach, the key findings he presented, and the research that still needs to be done on this approach.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

REFERENCES
1. Lawton SM, Chao TY, Zhang F, et al. Optimization of fluoroscopy guided ultrasound mediated gene delivery in canines for sustained FVIII expression. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland. Abstract #422