Risk assessment in gene therapy and somatic genome-editing: An expert interview study

Background

Innovation in gene therapy and genome editing raises high expectations for therapeutic breakthroughs. With the increasing maturity of the field, gene products using “gene transfer” technology, such as viral vectors, designer nucleases, incl. CRISPR/Cas, as the most recent, are frequently tested in clinical trials. Before such trials are launched, the anticipated risks and benefits of using gene transfer technologies must be evaluated to ascertain an ethical balance of risks and benefits.

Methods

We conducted semi-structured interviews with experts (n=15) in gene therapy/genome editing. We applied thematic text analysis to identify the qualitative spectrum of strengths, weaknesses, opportunities, and threats (SWOT) of a risk assessment approach to gene therapy/genome editing research based on a comprehensive set of nine mechanistic categories of adverse reactions combined with estimates of risk probability according to World Health Organization (WHO) adverse reaction terminology.

Results

Our study revealed a clear demand for a structured approach to risk assessment gene therapy/genome editing. The interviews indicate that the nine presented mechanistic categories may be helpful to structure this risk assessment prior to initiating a new study. The interviews revealed a broad spectrum of practice-oriented SWOT, described in detail in this manuscript.

Discussion

The here presented SWOT for a structured approach to risk assessment prior to clinical trials with gene therapy/genome editing inform the refinement and implementation of such standardized approaches and the discussion among researchers, regulators, and funders. To overcome potential weaknesses and threats in the application of such a risk-based approach, the mechanistic categories need to be case-sensitive and complemented by information on the validity of relevant animal models, long-term risks, and information about patient characteristics.