CMN Weekly (13 August 2021)
By: Karen O'Hanlon Cohrt - Aug. 13, 2021
- Research led by Jennifer Doudna at UC Berkeley has elucidated how the smallest known CRISPR-Cas system, CasΦ, recognises and cleaves double-stranded DNA. The researchers used cryo-electron microscopy to determine the structure of CasΦ in pre- and post-DNA-binding states. The findings were published in Nature Structural and Molecular Biology earlier this week. Last year, we interviewed two of the researchers involved in discovering the so-called tiny but mighty CasΦ. You can read that interview here.
- A team of researchers led by Hans Clevers at Hubrecht Institute and collaborators in Holland have used prime editing to correct the underlying mutations in cystic fibrosis in human intestinal organoids (or mini organs), by replacing the mutated sequence with the healthy sequence. The study, published in Life Science Alliance this week, shows that prime editing is safer than editing with CRISPR-Cas9 with respect to off-target edits, and lab results so far indicate restoration of function in gene-edited organoids. We interviewed Hans Clevers last year after his group published work showing that base editing could be used to correct cystic fibrosis-causing mutations in gut organoids. You can read that interview here.
- Allogene Therapeutics has received FDA Orphan Drug Designation for its gene-edited CAR T candidate ALLO-715 for the treatment of multiple myeloma. ALLO-715 is part of a pipeline of allogeneic CAR T candidates developed using Allogene's AlloCAR T platform that involves TALEN technology under licence from Cellectis. You can read more about ALLO-715 in our previous clinical roundup of gene-edited CAR T therapies.
- Nkarta Therapeutics, a biopharmaceutical company developing engineered natural killer (NK) cell therapies for cancer, reports second quarter 2021 financial results and business progress. The company expects to reveal Phase 1 clinical data on NKX101 for acute myeloid leukaemia and myelodysplastic syndromes later this year, as well as initiating dosing (Phase 1) for NKX019 in B cell cancers.
- Poseida Therapeutics reports program updates and financial results for the second quarter of 2021. The company, based in San Diego, is using a novel gene-editing and delivery platform to create curative therapies for cancer and genetic diseases, with two candidates in the clinic so far.
Industry quarter 2 financial updates
This week saw several additional quarter 2 finanical and business updates from companies working in the gene-editing space. You will find the highlights at the links below:
- Verve Therapeutics business, programme and financial update.
- Graphite Bio business progress and financial results.
- Precision Biosciences 2nd quarter financial results.
- Beam Therapeutics business, pipeline updates and financial results.
- CRISPR-associated transposase (CAST) systems, which are harnessed from cyanobacteria, use transposons to precisely and efficiently insert large DNA sequences into a genome. Researchers at Cornell University have now used cryo-electron microscopy to unravel a previously unexplained feature of CAST systems – that is, how they direct insertions in a single orientation at a precise distance from the programmed target sequence. The findings were published in Science today.
- To explore the effect of gene-editing on cardiac disease associated with Duchenne muscular dystrophy (DMD), researchers led by Eric Olson (University of Texas Southwestern) used CRISPR-Cas9 to target exon 45 of the DMD gene in order to generate corrected DMD in patient-derived cells, wherein the DMD open reading frame was restored via reframing (RF) or exon skipping (ES). They found that it was possible to correct dysfunctional DMD cardiomycyes (CMs) by adenoviral delivery of Cas9-gRNA and that correction of DMD CMs post-differentiation reduced their arrhythmogenic potential. They also showed that transcriptional dysregulation in CMs and fibroblasts in DMD mice could be restored to similar levels as wildtype mice following CRISPR-Cas9 targeting of exon 45. The findings were published in Circulation Research earlier this week. You can read more about how CRISPR is used to develop new therapies for DMD in our earlier article.
Pioneers and patents
- The CRISPR patent dispute is not over here. Read the latest update here.
- Pope Francis has appointed co-inventors of CRISPR and joint nobel Laureates in Chemistry, Jennifer Doudna and Emmanuelle Charpentier, to the Pontifical Academy of Sciences. Religious belief is not a criterion for membership in the pontifical academy, which is conceived as a place where science and faith can meet and discuss.
- The 4th International Conference on CRISPR Technologies. This virutal event scheduled for 1st-3rd October will assemble academics and industry representatives to highlight the cutting edge of these developments and the most immediate technical and societal changes. Topics will emcompass a broad range of CRISPR-Cas fields from discovery-based research, tool development, synthetic biology, and engineering. Registration information here.
- CRISPR and Beyond: Perturbations at Scale to Understand Genomes. A virtual conference hosted by Wellcome Connecting Science scheduled for 1st-3rd September 2021, that will explore methods to modulate the genome at scale. Registration details here.
- International Conference on CRISPR and Gene Editing (ICCG). This digital conference takes place from December 13th-14th, and aims to assemble academic researchers and scientists to share experiences and results on all aspects of CRISPR and genome editing. Abstract submission for posters and presentations is still open, see here for programme details.
- Gene drives gaining speed. Gene drives are selfish genetic elements that are passed down to progeny at super-Mendelian (>50%) frequencies. CRISPR-Cas9-based gene-drive systems have shown great potential for controlling the prevalence of vector-borne diseases, crop pests and non-native invasive species, but concerns reamin about their long-term effects in nature. This review summarises progress within CRISPR-based gene drives.
Huh, Heh, Wow
- CRISPR supersizes corn. Scientists are using gene editing to increase corn kernel row number. Brief news article in Nature Biotechnology this week.
Sickle Cell Disease, SCD
Hereditary Angioedema, HAE (NCT05120830)
View all clinical trials
Acute Myeloid Leukemia, AML, (NCT05066165)