Modified prime editor for gene therapy optimization

This technology is a DNA editing platform with a reduced payload size to allow adeno-associated virus (AAV) and nanoparticle packaging for gene therapy.

Unmet Need: Size-compatible genomic prime editing system

Mutations in short sequences or single bases in the human genome account for 89% of known pathogenic variants, implying a need for efficient and directable genomic editing. Current methods to edit small regions of DNA through a process called “prime editing” are contained within a DNA payload that is too large to facilitate many gene therapies. Reducing the size of the prime editing platform would permit packaging into a single adeno-associated virus (AAV), which would allow for safer and more efficient delivery strategies and expand the application of gene therapy to treat a broader variety of conditions.

The Technology: Smaller prime editing platform for improved gene therapy opportunities

This technology enables enhanced modification of a target nucleic acid by using a single subunit of the reverse transcriptase. By presenting a smaller size than conventional prime editors, this technology can be packed and delivered in a single adeno-associated virus (AAV). The smaller payload allows for more effective delivery of genetic therapeutics and could also be used in other genetic assays, such as RT-PCR. Delivery of the technology enhances the ability of researchers and clinicians to design, optimize, and test novel gene therapies for adaptation into next-generation therapeutics.

This technology has been validated with in vitro studies with different cell lines.

Applications:

• AAV-compatible gene therapy platform
• Nanoparticle-based gene therapy platform
• Research tool for prime editing of cells in cellular experiments
• Germline editing for generation of animal models
• Research tool for development of new prime editing strategies

Advantages:

• Size-compatible with AAV and nanoparticles
• Expanded range of gene therapy opportunities
• Expression of a single nickase gene rather than multiple
• Opportunity to expand thermostability, activity, and interactivity with template

Lead Inventor:

Peter Quinn, Ph.D.

Patent Information:

Patent Pending (US20250171810)

Related Publications:

• Wu WH, Tsai YT, Huang IW, Cheng CH, Hsu CW, Cui X, Ryu J, Quinn PMJ, Caruso SM, Lin CS, Tsang SH. “CRISPR genome surgery in a novel humanized model for autosomal dominant retinitis pigmentosa.” Mol Ther. 2022 Apr 6; 30(4): 1407-1420.

• Zuccaro MV, Xu J, Mitchell C, Marin D, Zimmerman R, Rana B, Weinstein E, King RT, Palmerola KL, Smith ME, Tsang SH, Goland R, Jasin M, Lobo R, Treff N, Egli D. “Allele-Specific Chromosome Removal after Cas9 Cleavage in Human Embryos.” Cell. 2020 Dec 10; 183(6): 1650-1664.

• Fischer MD, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Ochakovski GA, Klein R, Schoen C, Sothilingam V, Garcia-Garrido M, Kuehlewein L, Kahle N, Werner A, Dauletbekov D, Paquet-Durand F, Tsang S, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B. “Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial.” JAMA Ophthalmol. 2020 Jun 1; 138(6): 643-651.

• Wu WH, Tsai YT, Justus S, Cho GY, Sengillo JD, Xu Y, Cabral T, Lin CS, Bassuk AG, Mahajan VB, Tsang SH. “CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa: A Brief Methodology.” Methods Mol Biol. 2018; 1715: 191-205.

Tech Ventures Reference:

• IR CU22084

• Licensing Contact: Kristin Neuman