Carol Miao, PhD, on the Importance of Continuing Preclinical Research in Gene Therapy

“...Some information you cannot get from animal studies; you have to try it in people. But I think when there are problems, it really needs to go back to basic research and [you need to] figure out what is going on to see how we can make it safer—not just only efficient or effective—but it also has to be safer.”

In recent years, gene therapy has rapidly come of age, with multiple adeno-associated virus (AAV) vector-based genomic medicines hitting the market and many more investigational genomic medicines in the midst of or entering the clinical stage of development. Notably, AAV vector-based gene therapies for both hemophilia A and hemophilia B received FDA approval in the past year. As such, gene therapy-focused conferences, which once primarily showcased preclinical research, have begun to host more and more presentations of clinical data in recent years.

On the other hand, 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 have remained strongly focused on preclinical work. Their lab is currently engaged in preclinical studies on several nonviral and viral alternatives to AAV vector-based delivery including ultrasound mediated gene delivery, targeted delivery by lipid nanoparticles, and intraosseous delivery with lentiviral vectors into hematopoietic stem cells. At the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, investigators from the Miao Lab gave a total of 6 presentations covering their preclinical findings.

In an interview with CGTLive™, Miao spoke about the need to not lose sight of the importance of preclinical work in gene therapy amidst the boom of recent clinical progress. She acknowledged that although presentations of clinical findings are exciting and important in their own right, they can sometimes take away attention from preclinical studies that can be of great importance, especially when it comes to improving the safety of future genomic medicines.

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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.