Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic

Abstract

Editorial summaryGenome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refractory to other types of intervention. Here, we identify some of the major challenges for clinicians, regulators, and human research ethics committees in the clinical translation of CRISPR-mediated somatic cell therapy.

CRISPR in context: towards a socially responsible debate on embryo editing

“…Oversimplifying consensus. Well before He Jiankui's activities, genome editing was the subject of a plethora of high-level meetings, workshops, reports and position statements by groups ranging from national funding organisations to supranational political entities and learned societies (The Hinxton Group, 2015; Nuffield Council on Bioethics, 2016; National Academy Of Sciences; National Academy Of Medicine, 2017; Nicol et al, 2017;Garden and Winickoff, 2018). While these differ in their focus, e.g., whether they deal exclusively with human applications or consider genome editing in a variety of organisms, virtually all reports and statements call for robust public engagement in order to determine the trajectory of research and eventual applications ARTICLE PALGRAVE COMMUNICATIONS | https://doi.org/10.1057/s41599-019-0319-5 of the technique.…”

“…1 The potential for CRISPR and similar tools to make inheritable changes to human embryos, known as germline genome editing (GGE), is particularly challenging to regulate at the global level. Where human clinical applications of somatic (non-heritable) genome editing must proceed through a framework of costbenefit analysis, clinical trials and regulatory review prior to any marketing approval (Nicol et al, 2017), germline modifications are already being framed as an assisted reproduction technology (ART). Fertility services, which allow evaluation and selection of embryos bearing certain characteristics, including preimplantation genetic diagnosis and in some countries sex selection, are already provided through an array of largely private clinics in countries around the world (Spar, 2006;Whittaker, 2011) and some scientists (including He) have already indicated interest in opening IVF clinics specialising in embryo editing (Begley, 2019;Cohen, 2019).…”

Prioritizing Women's Health in Germline Editing Research

“…1,2,3,4 These discussions center on questions about how and why both modification and uterine transfer of human embryos occurred, why established ethical boundaries for human subject research were crossed, which safeguards could have prevented this violation from occurring, and which oversight mechanisms were ignored or evaded. 5,6,7,8 As science is an international endeavor, we must ask which bioethical frameworks should guide researchers from different countries and cultural backgrounds in a unified effort to conduct germline editing research in a way that reflects the goals and values of individuals, families, and societies. 9,10 Statements from leading scientists, policymakers, and ethicists agree that there must be robust and deliberate engagement of multiple stakeholders in order to responsibly govern these technologies.…”

Gene editing for advanced therapies

“…There are a number of challenges facing regulatory science in the field of advancing technology. Notably, many of the concerns are not new in and of themselves, but new technologies, such as CRISPR change their scope and scale (Nicol et al, 2017 [56] ). Many of the primary concerns will be centred on the pre-clinical to clinical transition, most notably through the uncertainty around the risk benefit dynamics of new technologies.…”

“…One of the US standards setting bodies, the National Institute of Standards and Technology (NIST) announced in mid-2017 the creation of a Genome editing Consortium (National Institute of Standards and Technology (NIST),(n.d.) [91] ). The Consortium aims to promote coordination between NIST and stakeholders within the gene editing community to advance standards for genome editing technology.…”