Cell and gene therapies hold tremendous value due to their efficacy and potency in a diverse range of indications. The classical approach to gene therapy involves the replacement of a defective gene by the delivery of a normal gene. A more recently developed strategy is to repair genetic defects by gene editing. The ability to edit the expression of a gene associated with a disease offers the most direct path for the development of therapeutics for thousands of inherited and acquired genetic diseases, such as cancers and viral infections.
Expediting these therapies at research level can require several essential tools, such as molecular cloning, plasmids, and viral vector systems, all of which must be carefully coordinated in order to design and produce functional therapies. To minimize the number of therapeutic products to be developed, one option is to deliver all the components required for gene editing by a single vector with an excellent safety and efficacy profile. AAV (adeno-associated virus) meets these requirements, except that its effective packaging capacity is only ~3,600 nucleotides, which is incompatible with most editing strategies. Therefore, designing efficient vectors is critical for gene therapy research.
This webcast will highlight editing by spliceosome-mediated RNA trans-splicing, which circumvents the AAV packaging limit problem. RNA trans-splicing molecules require only ~200 nucleotides for activity, leaving over 3,000 nucleotides that can be expressed by the edited mRNA. Another strategy for designing efficient vectors is to optimize the viral capsid to enable efficient cell entry while minimizing immune responses. These splicing-based strategies can be used to ensure safety and potency in both in vitro and in vivo settings.
Learn:
• Overview of AAV research tools and the AAV manufacturing process
• How to design effective AAV gene therapies using RNA trans-splicing as an editing strategy
• Optimization of AAV vectors to effectively deliver large constructs
Unable to join the live event? Watch on demand. Register now to ensure that you receive information on how to gain access after the live event.
This webcast has been produced by Charles River Laboratories, who retails sole responsibility for content. About this content.
Speakers
Lloyd Mitchell, CEO and CSO, Splice Therapeutics
Lloyd Mitchell, MD, is the CEO and CSO of Splice Therapeutics based in Maryland. Lloyd served at the National Institute of Mental Health (NIMH) for 8 years as a medical staff fellow, Senior Staff Fellow and Lieutenant Commander, US Public Health Services. In 1995, he founded Intronn and served as CEO/CSO for 9 years. He founded Splice Therapeutics in 2004 to find RNA editing technologies that can support gene therapies. He also served as Adjunct Associate Professor at Howard University College of Medicine for 9 years.
James Cody, Associate Director, Technical Sales and Evaluations, Charles River Laboratories
Since 2018, James Cody, PhD, has worked in the viral vector CDMO space for Vigene Biosciences, which was acquired by Charles River in 2021, and is a member of the business development team based at Rockville’s (MD) Viral Vector manufacturing site. In his current role, James provides technical support to the business development team, helping to onboard new projects by working in close collaboration with subject matter experts across various functional groups.
Moderator
Sarah Hiddleston, Nature Research Custom Media
Sarah Hiddleston is a freelance journalist who has worked with Nature Research Custom Media since 2015. Previously, Sarah worked for a decade in Madras (Chennai), India, specialising in health, pharmaceutical and environmental stories. Sarah holds an MA in Investigative Journalism from City University London, an MSc in Political Theory from the London School of Economics, and an undergraduate degree in History from the University of Cambridge, UK.
