Abstract
The dream of deploying CRISPR-based genome editing in patients to cure disease is now a reality. Results of a Phase I clinical study recently reported by a team from Intellia Therapeutics* and Regeneron Pharmaceuticals in the New England Journal of Medicine illustrate how CRISPR payloads can be deployed in vivo to alter the genome in liver cells and reduce transthyretin levels in patients with transthyretin amyloidosis (ATTR amyloidosis).
Impressively, a single dose was able to lower protein levels up to 96%. Details of that breakthrough clinical trial are discussed on page 460 of this issue by Kiran Musunuru in a First Cut article. Coming about 6 months after previous results showing success for ex vivo treatment of sickle cell and beta thalassemia patients, this study is being widely hailed for providing proof of concept of the therapeutic potential of CRISPR medicines for many patients afflicted by genetic diseases.
Critically, this de-risks the endeavor not only for academics and biotech companies but also for patients, clinicians, and regulators. This will embolden innovators such as Intellia, Editas Medicine, CRISPR Therapeutics, and Beam Therapeutics—as well as several companies that have recently gone public, including Verve Therapeutics, Graphite Bio, and Caribou Biosciences—to raise more capital, expand their clinical pipelines, diversify partnerships, and fuel the seeding of next-generation CRISPR companies. Notably, Prime Medicine recently came out of stealth mode, announcing a sizeable round of financing of more than $300 million.
Meanwhile, the dialogue about how we should safeguard and deploy somatic and potentially germline genome editing in humans continues to evolve. After 2 years' debate, the World Health Organization has finally issued its report on human genome editing, which is dissected in a First Cut by Lluis Montoliu on page 464. This extends and broadens to some extent the conversation about the implications of this disruptive technology. A valuable addition to this debate is a historical Perspective from LeRoy Walters, Robert M. Cook-Deegan, and Eli Y. Adashi (page 469).
Of course, this critical topic continues to drive studies cataloguing the opinions of diverse stakeholders—as we have consistently championed. Two new reports in this issue provide a view from the bench on governance (see page 609) and from the public as viewed from the Dutch DNA-dialogue project (see page 616). Given the pace at which CRISPR technology continues to evolve, the speed of progress in the clinic, and the continued expansion of the deployment of CRISPR tools across the tree of life (this issue's cover art illustrates the potential of genome editing in aquaculture), it is more crucial than ever to promote an inclusive and comprehensive dialogue.
Sadly, the continued anti-science sentiment remains a challenge for the CRISPR community. The need to engage various stakeholders with compelling storytelling remains crucial, and we hope our readers will continue to promote trust in genome-editing technologies in humans and beyond. We want to optimize and unleash these powerful tools and benefit not just from precision medicines, but also biotechnology, food, and agriculture across the globe.
We have written before about the democratization of CRISPR. In My CRISPR Story (page 467), we share a personal account of the trials and tribulations of implementing CRISPR by researchers in Pakistan. Their enthusiasm and determination are inspiring, and we hope that some readers may be able to provide further advice and support. We note enthusiastically that the papers published in this issue have been contributed from authors affiliated with organizations from Belgium, Canada, Germany, Israel, Japan, the Netherlands, Spain, and the Unites States. Following our previous special issue covering CRISPR in China, it is gratifying to see the collective CRISPR community continuing to transcend pandemic-related isolation and distance, in an inspiring interconnected network benefiting all.