36749 - Session I - Genome Editing

Genome editing is rapidly progressing into a new treatment paradigm for a wide range of human diseases. Its ability to permanently modify the target sequence allows the potential to achieve long-lasting or curative effects. Like every innovation, the clinical use of genome editing technologies comes with its own challenges.
Speakers will address the most critical aspects to consider in the design and control of the different genome editing tools to improve specificity and avoid genotoxicities. As important differences are expected for in vivo vs ex vivo applications, both approaches will be covered.
Phillip Ramsey will provide an overview of genome editing platforms, on-target safety evaluation, off- target identification, and provide recommendations on how to assess these potential risks and how to minimize these risks from a CMC perspective.
Jonathan Phillips will present an overview of therapeutic CRISPR/Cas9 genome editing, using NTLA-2001 as an example with a focus on the assessment of mutagenicity (off-target) and chromosomal structural integrity, followed by a discussion of genetic safety considerations and approaches.
Cicera Lazarotto will discuss the risks of inadvertently introducing oncogenic off-target mutations and present sensitive analytical methods, such as GUIDE-seq, CHANGE-seq, and Digenome-seq, for defining the genome-wide activity of genome editors, to better understand the features that drive the genome-wide activity of engineered nucleases, and the frequency and location of resulting off-target mutations.