Introduction to gene-directed therapies (a LinkAGE webinar)
Channel: Genomics Education Programme
Date: 2023-02-02

This LinkAGE webinar provides an introduction to gene-directed therapies and is presented by cellular therapeutics expert Dr James Patterson. We have provided timestamps, video chapters and transcriptions (coming soon) to help you find what you need. The webinar and Q&A was broadcast live on 24 January 2023 and covered:

- an introduction to gene-directed therapy modalities and strategies (19:34 onwards);
- the use of genetic approaches for ex vivo engineering of therapeutics (28:48 onwards);
- how we deliver gene medicines in vivo (40:13 onwards);
- novel in vivo gene-directed therapeutics for complex disease (42:52 onwards); and
- a discussion of near-term advancement and an overview of key challenges facing next generation approaches (25:17 and throughout).

Learning objectives for the webinar include being able to:
- Summarise different gene-directed therapy modalities and strategies.
- Identify different genetic approaches used for ex vivo engineering of therapeutics.
- Explain how we deliver gene medicines in vivo.
- Describe how novel in vivo gene-directed therapeutics are used for complex diseases.
- Discuss near-term advancements in gene-directed therapeutics and the challenges that they may present.

What is the LinkAGE expert webinar series?
The Genomics Education Programme's LinkAGE (Linking Academia and Genomics Education) series will aim to provide expert seminars on exciting ‘bench-to-bedside’ projects that are likely to impact on clinical practice in the not-too-distant future.

Who is the LinkAGE expert webinar series aimed at?
This webinar series is aimed at researchers, clinicians and other healthcare professionals who already have a strong understanding of fundamental genomics concepts. If you are just starting your learning journey, or need a quick refresher, we encourage you to visit our website: www.genomicseducation.hee.nhs.uk

Meet the speaker
James Patterson, MB/PhD, currently works in Cambridge, UK on his start-up Xap Therapeutics. James studied medicine at Cambridge, where he spent most summers working on a diverse set of projects, from worms to cancer stem cells. He graduated with a degree in medicine/biochemistry before moving to the Francis Crick Institute to complete his MB/PhD on fission yeast cell size control with the Nobel prize winner Sir Paul Nurse. Separate to his academic work, James developed and built an IP focused biotech company – Auxolytic – which demonstrated proof of concept of a CRISPR-engineered cell therapy safety switch. In 2018, James founded Xap Therapeutics, a biotech company developing a CRISPR engineered, iPSC-derived delivery vehicle for complex therapeutics.

TIMESTAMPS
00:00 Welcome and introductions
02:28 Contents and scope of webinar
04:03 Gene-directed therapies: an introduction
06:34 What is gene expression?
11:10 How does a cell 'decide' what genes to express?
19:34 How to target to a gene expression pathway?
24:03 How are gene-directed therapies delivered?
25:17 Issues in delivery: cell-autonomous and payload immunity
28:48 Ex vivo delivery: haematopoietic stem cells (HSC)
32:54 Ex vivo delivery: lentivirus
35:12 Ex vivo delivery: CRISPR therapeutics
38:23 Ex vivo summary
40:13 In vivo therapeutics and administration challenges
42:52 In vivo: AAV
46:12 In vivo: siRNA
49:43 Q&A and close