CMN Weekly (7 May 2021)

Top picks

• Researchers in Germany have developed a multiplexable diagnostic platform known as LEOPARD (Leveraging Engineered tracrRNAs and On-target DNAs for PArallel RNA Detection). LEOPARD allows simultaneous detection of RNAs from different viruses in one test and could distinguish SARS-CoV-2 and its D614G variant with single-base resolution in patient samples. The findings were published in Science last week.
• CRISPR’s Next Frontier: Treating Common Conditions. Popular piece from Wall Streeet Journal that discusses how gene editing might not just help people with rare disorders but millions of others with heart disease, chronic pain and other conditions, in the decade to come.

Industry

• CRISPR Therapeutics and Nkarta Therapeutics announce global collaboration to co-develop two new CRISPR-Cas9-edited CAR natural killer (NK) cell therapies for cancer. The agreement also grants Nkarta with a license to use CRISPR Therapeutics' CRISPR technology to edit five gene targets in an unlimited number of Nkarta’s NK cell therapy products.
• Metagenomi to share five presentations at the 24^th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) to be held virtually next week. The presentations will reveal pre-clinical data about the company’s novel CRISPR-associated gene-editing systems, CRISPR-associated transposases (CAST) system, and the use of these systems for ex vivo and in vivo therapy development.
• Precision BioSciences presented a paper at the Association for Research in Vision and Ophthalmology 2021 Annual Meeting earlier this week. The paper highlighted Precision’s pre-clinical research using its meganuclease-based ARCUS® genome-editing platform for autosomal dominant Retinitis Pigmentosa (adRP). You can view a recording of that presentation here.
• Industrial biotech company BRAIN Biotech Ag (Germany) has developed a novel CRISPR-Cas tool using metagenomics sequencing and protein engineering. The tool is a non-Cas9 nuclease that has been validated in numerous microorganisms and is currently being tested and validated in plants and mammalian cells. The company has submitted an IP application to protect the undisclosed nuclease sequence.

Quarter 1 industry update highlights

• Editas Medicine: Initial clinical data for the first in vivo CRISPR therapy EDIT-101 in Phase 1/2 BRILLIANCE trial for the treatment of LCA10 is expected later this year. The company also plans to progress clinical studies for Cas12-edited EDIT-301 in haemoglobinopathies this year.
• Fate Therapeutics: Highlights include a positive financial update, and that Phase 1 data from the FT516 and FT538 programmes in relapsed and refractory acute myeloid leukaemia (AML) is expected in conjunction with the ASGCT meeting next week.
• Intellia Therapeutics expects to submit an IND or equivalent for its CRISPR-edited T cell therapy NTLA-5001 for AML in mid-2021. Initial safety and activity data from a Phase 1 trial for NTLA-2001 is also expected mid-2021. NTLA-2001, developed in partnership with Regeneron, is the first systemically delivered CRISPR-based therapy, and is designed as a single-dose cure for the rare genetic disease transthyretin amyloidosis.
• Sangamo Therapeutics: The company received fast track designation from the FDA for SAR445136 (formerly known as BIVV003) in Q1. SAR445136 is a zinc finger nuclease (ZFN)-edited cell therapy candidate for the treatment of sickle cell disease, developed in collaboration with Sanofi. The European Medicines Agency (EMA) has also granted orphan designation to SAR445136 based on early clinical data from three treated patients.
• Allogene Therapeutics: Data expected on ALLO-501 ALPHA and ALLO-501A ALPHA-2 trials at the American Society of Clinical Oncology (ASCO) Annual Meeting in June. Allogene has also initiated its first solid tumour trial (TRAVERSE) for ALLO-316 (anti-CD70 CAR T) in advanced or metastatic renal cell carcinoma.

Research

• Scientists from the Wyss Institute at Harvard have created a new gene-editing tool called retron library recombineering (RLR) that might rival CRISPR. RLR is a high-throughput method with multiplex capabilities that exploites the targeted reverse-transcription activity of retrons to produce ssDNA in vivo. The method was shown to incorporate edits at >90% efficiency. The findings were published in PNAS this week. You can also catch a writeup of the study at Wyss Institute's website.
• Researchers at Duke University retrospectively examined sequence features that impact gRNA activity in 39 published data sets, and uncovered strong evidence that the genomic context greatly influences differences in gRNA-dependent activity in CRISPR editing. The authors defined context as the DNA content outside of the gRNA/target sequence and hope that the findings will contribute to better understanding of Cas9 activity and optimisation of gRNAs and Cas variants. The results were shared on bioRxiv yesterday.
• A team in China has developed TB-QUICK, a DNA detection platform for Mycobacterium tuberculosis that combines loop-mediated isothermal amplification (LAMP) and CRISPR-Cas12b detection. Initial results reveal potential for rapid and sensitive detection in pulmonary and plasma samples but the clinical application needs to be assessed further. The results were published in the Journal of Infection this week.
• Researchers demonstrate ligand-induced activation of CRISPR-Cas9 function by integrating a theophylline aptamer into protein-unrecognised regions of gRNA. This design of allosteric regulation creates an opportunity for conditional control of CRISPR-Cas9 function using specially designed gRNAs. The findings were published in Chemical Communications earlier this week.

COVID-19

• Sherlock Biosciences’ CRISPR SARS-CoV-2 test selected as a finalist in “On the Rise” and received an honorable mention in the “Health and Pandemic Response” Categories of Fast Company’s 2021 World Changing Ideas Awards. Last year, Sherlock Biosciences became the first company ever to obtain FDA authorization for a CRISPR product, when it received Emergency Use Authorization (EUA) for its COVID-19 test kit. We interviewed Sherlock’s CEO last year to hear about the test and the underlying SHERLOCK technology platform.
• Researchers in Peru recently clinical validation data for the RCSMS workflow for rapid SARS-CoV-2 detection from from saliva. The RCSMS workflow is locally-adapted variant of Mammoth Biosciences’ CRISPR-Cas12a DETECTR platform, which involves a thermochemical treatment with a detergent to inactivate viral particles and nucleases in saliva, thus bypassing the need for expensive viral RNA isolation. Their test revealed sensitivity and specificity of 93.8% and 99%, respectively. The findings were recently shared on the preprint server medRxiv.

Delivery

• Overview and Update on Methods for Cargo Loading into Extracellular Vesicles: Review that summarises and discusss the pros and cons of methods used for cargo loading into extracellular vesicles, including CRISPR/Cas9, mRNAs, proteins, and othe cargoes. Extracellular vesicles are naturally-occuring phospholipid bilayer-enclosed vesicles secreted from all cell types. They interact intrisically with the plasma membrane and are gaining much attention as a natural drug carrier.

Webinars

• Don't miss CRISPR Medicine News webinar on May 26th. We have 4 excellent speakers lined up to discuss the huge topic of CRISPR Delivery Systems. Find out more and sign up to attend here.

Conferences

• SYNTHETIC BIOLOGY BIOPHARMA CONFERENCE 2021. A one-day event on 26^th May that looks at how 2020 transformed the biopharma industry and what new technologies and diagnostic tools are continuing to accelerate drug discovery. Speakers include a mix of representatives from drug developers, suppliers and venture firms. See website for more details.

Awards

• The US National Academy of Sciences recently announced the election of 120 new members, including CRISPR and base editing pioneer David Liu from Broad Institute of Harvard and MIT. See the full list of new members here.

Ethics

• He Jiankui´s gene-editing experiment and the non-identity problem: a bioethics analysis of He Jiankui's case in relation to one of the most difficult problems in procreative ethics (or the ethics of future generations): the non-identity problem. The non-identity problem was introduced by British philosopher Derek Parfit in the 1980s and it is said to arise when our actions in the present could change which people will exist in the future, for better or worse.