Carol Miao, PhD, on Bringing Together Novel Gene Editing Tools and Delivery Methods

“...I'm actually very excited to see there’s lots of development on these genetic editing tools being reported in this meeting. I think a combination of that with our delivery strategy that we have improved over the years—that's going to be able to produce a safe and effective therapy for treating patients with genetic diseases.”

Recent FDA and European Medicines Agency approvals of adeno-associated virus (AAV) vector-based gene therapies for indications including hemophilia A and hemophilia B have provided transformative new treatment options for many patients. Although, AAV-based approaches come with an inherent limitation: if efficacy of an AAV vector-based gene therapy drops over time, redosing can be difficult or impossible due to the presence of antiAAV antibodies in patients’ bodies. As such, there is interest in developing alternative delivery methods for genetic medicines, even for indications that already have an approved AAV vector-based gene therapy on the market, in order to enable redosing, if it becomes necessary.

Carol Miao, PhD, a principal investigator at Seattle Children’s Research Institute, and a professor in the Department of Pediatrics at the University of Washington School of Medicine, and her colleagues are currently conducting preclinical research on several nonviral and viral alternatives to AAV vector-based delivery, with a specific focus on delivering gene editing tools for the management of hemophilia A. Investigators from her lab gave a total of 6 presentations regarding the lab’s research at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.

In an interview with CGTLive™, Miao discussed the promise of nonviral gene replacement therapy and gene editing, noting that nonviral gene replacement therapy may serve as an intermediate solution to the limitations of AAV vector-based approaches while the safety of gene editing methods are evaluated further. With regard to her own lab, which is researching methods including ultrasound mediated gene delivery, targeted delivery by lipid nanoparticles, and intraosseous delivery with lentiviral vectors into hematopoietic stem cells, Miao stated that they are seeking partners to help bring their programs to clinical trials.

Click here for more coverage of ASGCT 2023.

REFERENCES
1. Lawton SM, Fan MN, Chao TY, et al. NHEJ gene editing of hemophilia A mice show therapeutic levels of FVIII following ultrasound mediated gene delivery of CRISPR/Cas9 plasmid. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #31.
2. Chen CY, Cai X, Miao CH. Liver-specific targeting CRISPR/Cas9 mRNA LNPs achieve long-term FVIII expression in hemophilia A mice. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #26.
3. Rementer CW, Li C, Nichols TC, et al. Treatment of canine hemophilia A via intraosseous delivery of a platelet-specific factor VIII-lentiviral vector. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #632.