Скачать или смотреть Advancing Gene Therapies through Targeted mRNA Delivery and Scalable CRISPR Solutions

Precision to Production: Advancing Gene Therapies through Targeted mRNA Delivery and Scalable CRISPR Solutions

Abstract:
This talk bridges cutting-edge innovations in mRNA delivery systems with scalable, regulatory-compliant CRISPR tools to address the dual challenges of precision and practicality in gene therapy development.

Part 1: Targeted Lipid Nanoparticles loaded with mRNAs for Gene Editing

Recent advancements in RNA therapeutics highlight the potential of mRNA-based tools for in vivo gene editing with lipid nanoparticles (LNPs) co-loaded with gene-editing enzymes and sgRNA, offering a safer alternative to traditional methods. A key challenge is achieving efficient, tissue-specific delivery. We optimized LNP formulations for targeted delivery to T cells and hepatic cells, significantly enhancing protein expression and gene-editing efficiency. Our ReadyEdit platform supports prime editing, base editing, and Cas enzyme applications at clinically relevant loci like PCSK9 and TRAC. Our LNPs have achieved over 60% editing efficiency in HEK293T cells and 20% in liver cells. Codon optimization of enzyme-coding mRNA resulted in a fivefold increase in expression, maximizing the potential of mRNA-based gene editing. These findings hold significant potential for advancing research in RNA-based therapeutics.
     
Part 2: Securing the CRISPR Pipeline with Scalable cGMP Guide RNA

The promise of CRISPR-based therapies hinges on reliable, high-quality reagents. GenScript addresses this need with scalable cGMP guide RNA (gRNA) production tailored for diverse CRISPR systems—Cas9, Cas12a, prime editing, and base editing. We will detail our state-of-the-art manufacturing infrastructure, featuring dedicated production lines, rigorous quality control, and rapid 30-day clinical-grade gRNA synthesis. We will also explore how comprehensive regulatory support, including Drug Master Files (DMFs) and IND-enabling documentation, accelerates therapeutic development. Case studies highlight partnerships with biotech innovators to streamline workflows from preclinical validation to commercial-scale production.

Speaker 1: Dr. Shambhavi Shubham
Title: Sr. Research Scientist
Company: GenScript
Bio: Dr. Shambhavi Shubham is an accomplished scientist with 10+ years of expertise in CRISPR editing, prime editing, mRNA solutions, and NGS technology. Currently, Dr. Shubham is a Senior Scientist II at GenScript, leading gene editing and mentoring teams. Former Principal Scientist at Salish Bioscience, driving R&D for next-gen liquid biopsy assays. Extensive experience in developing DNA aptamers, enzyme kinetics, and novel assays for cancer research and diagnostics. Strong background in cross-functional collaboration and project management. Proven ability to innovate in molecular biology, genomics, and biotechnology, with a strategic perspective from previous roles in licensing and technology commercialization.

Speaker 2: Dr. Jianpeng Wang
Title: Senior Director of GMP Production Dept.
Company: GenScript
Bio: Dr. Jianpeng Wang received his doctor’s degree in chemistry from the Chinese University of Hong Kong, he has more than 15 years’ experience in peptide & nucleic acid chemistry and filed 20+ patents. Since joining GenScirpt in 2015, Dr. Jianpeng Wang has led the nucleic acid R&D and manufacturing departments to develop, launch and deliver the nucleic acid reagents for CRISPR. Specifically for the guide RNA, Dr. Jianpeng Wang led the GenScript team to deliver more than 120 GMP batches, supported 40+ clinical programs, and got 13 global IND approvals.