A CRISPR Focus on Attitudes and Beliefs Toward Somatic Genome Editing From Stakeholders Within the Sickle Cell Disease Community

As sickle cell disease (SCD) affects millions of people worldwide, it will likely be one of the first targets of CRISPR-mediated somatic genome editing. Those living with SCD have limited treatments available to them despite the disease having been identified over a century ago and posing a significant global health burden. Affected individuals inherit 2 abnormal copies of a single pathogenic variation (A -> T) in the sixth codon of the beta-globin gene, resulting in the production of malformed hemoglobin. As SCD is a well-studied molecular disorder impacting the blood system, it comprises an ideal candidate for gene editing therapies. As previous studies have concluded that genome editing interventions cannot succeed without input and support from patient communities, this study sought to capture the perspectives of key stakeholders in the SCD community toward CRISPR-mediated somatic genome editing. Fifteen focus groups were conducted in the Southern and Mid-Atlantic regions of the United States between April 2017 and December 2017, including 6 patient groups, 6 parent groups, and 3 physician groups. Participants were recruited through collaborations with hematologists, community-based SCD organizations, and at national SCD conferences. Forty-six patients, 41 parents, and 23 hematologists participated in the study. The majority of patients (88%) and parents (85%) self-identified as African American and/or black. All 3 stakeholder groups were hopeful that gene editing could provide the overdue, impactful treatment for SCD many have been waiting for, given the current lack of treatment for SCD in comparison to treatments for other diseases. Other motivating factors included altruism for finding a cure for others and perceived shortcomings of existing treatments. Deterrents for the study included time commitments, fear of potential complications, and the permanence of the CRISPR procedure. Parents also often feared making a decision that could potentially exacerbate their child's condition, as well as inhibiting reproductive viability of their children. Participants expressed apprehension for the research enterprise's trustworthiness and transparency, although there was some confidence in the regulatory bodies governing the enterprise. Additional concerns included both religion and age. Some patients felt that it was "playing God" to edit genes with CRISPR, while others believed that God intended the procedure to help improve lives. Other patients expressed apprehension that the procedure would have been more beneficial in a younger stage of life, but participation would now be too difficult. Despite varying concerns, however, all stakeholder groups found it important to determine conditions and critical windows for maximal effectiveness of the procedure. Ultimately, patients, parents, and physicians expressed fear of community exclusion from the long-term benefits of research. A pervasive concern existed among all groups that SCD patients might be used to help validate and improve the tool's utility, after which profit-based incentives and efforts to treat other diseases could overshadow those who risked their lives to make these therapies a reality. The search for curative treatments using gene editing has provided renewed hope across the SCD community, enabling the visualization of a future with less pain, stigma, and neglect. With that hope also lies cautionary undertones, in part due to the medical disenfranchisement of the SCD community.