Carol Miao, PhD, on Exploring New Delivery Methods for Gene Replacement Therapy and Gene Editing


The principal investigator at Seattle Children’s Research Institute discussed the preclinical research on delivery methods for genomic medicines that her lab presented at ASGCT’s 2023 meeting.

“...What we're focusing on is how to improve the delivery, the transgene expression cassettes, and the cargo that is being delivered. All this is to try to improve the efficiency of gene delivery. Whether it's for gene replacement therapy or gene editing, these are all very big issues that need to be addressed. I actually am very impressed with all the CAR T-cell [therapies]—now they use gene editing technology to make these CAR T-cells—as well as a lot of new developments with gene editing tools. But no matter what we develop in all these strategies, still we have to deliver them into the correct target tissue...”

Delivery methods remain an important area of interest in the genomic medicine space. Thus far, the field has made substantial use of adeno-associated virus (AAV) vector-based approaches for delivering gene therapies. Although AAV vector-based delivery methods are used in several FDA-approved therapies and a very large number of investigational gene therapies, these methods have several limitations. To overcome drawbacks such as imprecise tissue targeting and immune system reactions, many investigators are now looking into alternative options.

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, is currently evaluating several nonviral and viral alternatives to AAV vector-based delivery, with a specific focus on gene delivery and gene editing for the treatment of hemophilia. Investigators from her lab gave a total of 6 presentations detailing 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 challenges of delivery for gene therapy and gene editing and her lab’s research in this area. She specifically noted that her team is doing preclinical research with ultrasound gene delivery, targeted delivery by lipid nanoparticles, and intraosseous delivery with lentiviral vectors into hematopoietic stem cells.

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.
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