Project: Off-Target Effect Analyses for Gene Editing Products

Type: Pre-Standard Research project

Partners: The SCB Gene Therapy Sector Working Group

Description:

The genome editing community lacks sufficient best practices for assessing off-target effects (i.e., unintended genetic modifications). There is a lack of technical understanding and agreement surrounding how much of the genome needs to be sequenced when looking for off-target effects, as well as how much confidence to have in the result based on the percentage of the genome that was sequenced. The community also lacks a framework for validating new methods to ensure they produce valid and consistent results. A standard in this area could help organizations avoid spending significant time and resources testing measurement methods and designing method validation approaches in house. Arriving at proven, reliable measurement approaches for detecting off-target effects would also improve patient safety and foster public confidence in gene-edited therapeutics.

As a precursor to standard advancement, SCB is coordinating development of a white paper on common off-target analysis challenges and solutions.

Progress:

Established a Working Group: SCB has assembled a working group to explore the potential for new standards for off-target effect analysis.

Conducted a Feasibility Assessment: In April 2021, SCB organized a series of meetings of experts from multiple stakeholder groups to discuss barriers and opportunities for potential standard topics for gene delivery methods and gene editing tools. A single standard is unlikely able to address all relevant issues in the genome editing field. However, the feasibility assessment group identified off-target effect analysis as a high-priority subtopic and proposed that an appropriate first step would be to develop a white paper on the sub-topic. More input is needed from the community to identify an appropriate scope for a standard; SCB is currently seeking feedback on the feasibility report.

Drafting a white paper: Input gathered during white paper development will help inform creation of a standard better tailored to real-world needs and best practices and more likely to be embraced by the community. Specific white paper aims are to clearly define the challenges faced by the community and to seek consensus on the models for in vivo gene editing, the necessary areas of the genome to sequence and analyze, and methods for data interpretation, among other related topics.

Get Engaged:

SCB needs subject matter experts like you to join the working group. To help, please contact SCB.