Updates on CRISPR therapy development and clinical trials
When I first heard of CRISPR gene editing I was excited for my lab to try it out, but it seemed a long way from the field having even one CRISPR therapy available to treat human disease.
In the Knoepfler lab, we study genetic and genomic programming in human development and disease. Gene editing seemed like a great tool for us moving forward. And it has been. Of course, I’d heard of designer ZFNs and TALENs. My colleague here at UC Davis, David Segal, and his trainees had given talks on their work in that area back then.
Back in 2014 when I first started thinking more about it, CRISPR seemed a whole lot simpler.
What I didn’t imagine in those days was that there would be so many gene-editing clinical trials ongoing already in 2022. Today’s post is an update on some recent developments, both encouraging and in some ways discouraging.
There’s been some discussion lately about the possibility of CRISPR designer babies, but that’s a topic for another post. As regular readers here will know, I’ve regularly discussed that topic. You might check out my book GMO Sapiens, which is focused primarily on potential heritable use of CRISPR in people.
In this post, I’m just focused on somatic efforts.
Remarkably, I found 124 trial listings on Clinicaltrials.gov for a search for those listing either CRISPR or gene editing. Not all of them are active or interventional, but it’s still a huge number given the relative newness of this field. I’m excited about many of these trials, but the development of CRISPR sickle cell therapies is a particularly compelling area.
CRISPR trial news
- CRISPR cancer trial success paves the way for personalized treatment, Nature. This complex clinical study designed T cells to recognize multiple cancer antigens at the same time. “Each of the 16 participants received engineered T cells with up to three different targets. Afterwards, the edited cells were found circulating in their blood, and were present in higher concentrations near tumours than non-edited cells had been prior to the treatment. One month after treatment, five of the participants experienced stable disease, meaning that their tumours had not grown. Only two people experienced side effects that were probably due to the activity of the edited T cells.” Here’s the original Nature research article: Non-viral precision T cell receptor replacement for personalized cell therapy.
- Editas halts lead CRISPR program after efficacy data underwhelm, Endpoints. Most participants had no benefit and the few that saw apparent benefits were homozygous, a much rare condition for this eye disease. It’s early days for gene-editing therapy development and developing any new therapy is extremely challenging. There are going to be ups and downs for this arena overall. I believe several safe and effective new gene-editing-based therapies will have a major impact. The timeline? It could take longer than any of us had hoped, but it’s going to happen.
- Perfection is too high a bar for CRISPR treatments, says STAT Biomedical Innovation Award winner David Liu, STAT News. This is a highly sensible interview with gene editing pioneer David Liu. He and his team developed base editing and prime editing. One challenge with clinical trials is that you need near perfection on the safety front at least. I recently included news of a participant death in a CRISPR trial in my recommended reads post. The cause of death is unknown.
- CRISPR’s ‘ancestry problem’ misses cancer targets in those of African descent, Science. Our field doesn’t have enough reference genomes from diverse populations. This is a limitation on applicability of CRISPR and even its accuracy in many cases. Here’s the source research preprint: Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries. The problems here extend into lab research too as depending on the cells we are using, they could have different sequences at gene editing target loci from the reference genome.