CMN Weekly (16 July 2021)

Top picks

• Researchers in the US deploy in utero adenine base editing to correct multi-organ pathology in Mucopolysaccharidosis type I (MPS-IH, Hurler syndrome), a lethal lysosomal storage disease. Findings from the proof-of-concept study, which was conducted in a mouse model, were published in Nature Communications this week.
• With fewer than 400 progeria patients worldwide, testing a CRISPR cure will be challenging. Opinion piece published in STAT News this week that examines the logistical and ethical challenges involved in clinically testing CRISPR treatments for this fatal genetic disease.
• Spotlight Therapeutics: making CRISPR deliver in vivo. A news feature published in Nature Biotechnology this week looks at California-based Spotlight Therapeutics, who are conjugating Cas proteins to agents that will home endonucleases and their guide RNAs to targets in vivo.

Clinical news

• Caribou Biosciences announces dosing of the first patient in a Phase 1 trial to evaluate CB-010, a CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy for the treatment of relapsed or refractory B cell Non-hodgkin lymphoma. This is the first allogeneic CAR-T cell therapy with a PD-1 knockout to reach clinical stage and initial trial data is expected next year.

Industry

• Prime Medicine launches with $315 million in financing to deliver on the promise of prime editing to provide lifelong cures for genetic diseases. Prime editing technology can be thought of as a DNA word processor that can “search and replace” disease-causing genetic sequences at their precise location in the genome, without resulting in double-strand DNA breaks. The company was founded by David R. Liu, PhD and Andrew Anzalone, MD, PhD. Learn more about prime editing in our interview with Andrew Anzalone from last year.
• San Francisco-based NKARTA establishes new combined natural killer (NK) cell therapy manufacturing facility and company headquarters. NKARTA’s technology is based on engineered NK cells to treat a range of cancers with two candidates at IND/clinical stage and plans to include CRISPR-Cas editing it its developmental pipeline.
• German BRAIN Biotech AG has so far identified around 2,000 untapped additional Class 2 CRISPR nucleases using metagenomics sequencing approaches, which could be deployed for genome editing. The company has so far analysed a limited number of these in detail and has already filed a first IP protection for 15 nucleases. BRAIN recently announced a prime candidate, which it dubs BRAIN Engineered Cas Nuclease (BEC), which is already applied in different organisms and projects.
• Seattle-based Shape Therapeutics has raised $112M in bid to make RNA editing a reality, just two years after the company spun out of Prashant Mali’s lab at University of California San Diego. Shape’s RNA-editing technology exploits ADAR, an enzyme that naturally occurs in human cells. The idea is that a researcher can apply a specially constructed strand of guide RNA to recruit ADAR, directing it to manipulate specific strands of mRNA by either adding or deleting bases as desired. The company’s main focus is neurons, where ADAR is abundant and efficient.

Research

• Mutations in the fukutin-related protein (FKRP) gene result in a broad spectrum of muscular dystrophy (MD) phenotypes, including the severe Walker-Warburg syndrome (WWS). A team in the US has now developed a gene-editing approach that replaces the entire mutant open reading frame with the wild-type sequence to universally correct all FKRP mutations in patient-derived induced pluripotent stem cells with encouraging in vitro and in vivo results upon implantation of the corrected stem cells into a murine disease model. The results were published in Cell Reports this week.

COVID-19

• Australian researchers report reprogramming of CRISPR-Cas13b to prevent SARS-CoV-2 transmission by targeting accessible regions of spike and nucleocapsid transcripts with >98% silencing efficiency in virus-free models. The team also showed that further optimised and multiplexed Cas13b CRISPR RNAs could suppress SARS-CoV-2 replication in infected mammalian cells, including the B.1.1.7 (UK) variant. The findings were published in Nature Communications this week.
• Researchers in Canada have developed a method for CRISPR-Cas12a-mediated gold nanoparticle aggregation that allows colorimetric detection of the N gene and E gene of SARS-CoV-2 in 45 min. The results were published in Chemical Communications this week.

Reviews

• Review of applications of CRISPR-Cas9 gene-editing technology in cancer research. A review of the current applications of CRISPR-Cas9 gene-editing technology in cancer studies, as well as the challenges faced and existing solutions.

Regulation

• A panel of experts from the WHO met this week and called on the world’s nations to impose stronger limits on human gene-editing experiments with a new set of guidelines. The new guidelines were heavily prompted by the case of He Jiankui (CRISPR babies). Read more in this New York Times writeup.

Podcasts and resources

• Kiana Aran PhD, Chief Scientific Officer at Cardea Bio, features in this recent Finding Genius Podcast, where she talks about how CRISPR Chip technology and biology may lead to the next generation of electronic sensors. Listen to the podcast here.
• Free guide RNA design tool and ICE v2 CRISPR Analysis Tool from Synthego Corporation.
• CROTON (CRISPR Outcomes Through cONvolutional neural networks) is a new automated and variant-aware deep learning framework for predicting CRISPR-Cas9 editing outcomes. The resource, developed at Hunter College High School (New York), Flatiron Institute (New York), and Princeton University (New Jersey), is available here.