CMN Weekly (8 April 2022) - Your Weekly CRISPR Medicine News

Top picks

• The long-standing CRISPR patent dispute is not completely over yet. This week, it was revealed that Nobel Laureate Emmanuelle Charpentier Ph.D., the University of California, Berkeley and the University of Vienna have officially appealed to the U.S. Court of Appeals for the Federal Circuit to review the recent decision from the U.S. Patent and Trademark Office, which ruled in favour of the Broad Institute of MIT and Harvard.
• The creator of the CRISPR babies has been released from a Chinese prison. He Jiankui, the Chinese scientist that created the first gene-edited children, was recently released from prison after serving 3 years.

Research

• Researchers in the U.S. and Italy report the seamless correction of the W1282X CFTR (cystic fibrosis (CF)) mutation using CRISPR-Cas9 nickases (Cas9n) in induced pluripotent stem cells derived from a CF patient homozygous for the W1282X Class I CFTR mutation. They describe gene correction by two independent processes: treatment with the PiggyBac (PB) transposase in vector replacements or by intrachromosomal homologous recombination between the tandemly duplicated CFTR gene sequences. The findings were published in Frontiers in Genome Editing earlier this week.
• In an article recently published in Nature Communications, researchers at various institutions in the U.S. report using CRISPR gene-editing technology in primary human T cells to reveal new host factors that alter HIV infection. They discovered more than 20 factors that were not previously described to play a functional role in HIV replication. The findings open up new possibilities for understanding HIV biology that may pave the way for new therapies.
• Researchers in the U.S. report in Molecular Therapy Oncolytics earlier this week that CRISPR-Cas12a knockout of miR21 reduced glioma growth and led to increased survival in immunocompetent mouse models of glioma. miR21 is a non-coding transcript that is involved in regulating gene expression in multiple cellular pathways, including proliferation. High expression levels of miR21 have been shown to be a major driver of glioma growth. The findings indicate that miR-21 may be a potential target for CRISPR-based therapeutics in glioma.
• In an article published in Genetics yesterday, scientists in the U.S. report the findings of a study to explore the generation of indels in the germline and somatic cells in female gene-drive lineages using a series of selective crosses between a gene-drive line, AgNosCd-1, and wild-type mosquitoes. They report that potential drive-resistant mutant alleles are generated largely during embryonic development, and that these are most likely caused by deposition of the Cas9 endonuclease and guide RNAs in oocytes and resulting embryos by homozygous and hemizygous gene-drive mothers. The discovery may contribute to solving one of the challenges for current Cas9-based drive systems, that is their ability to produce drive-resistant alleles resulting from insertions and deletions.
• A team in France report in mBio this week that ribonucleoprotein (RNP)-based CRISPR-Cas9 targeting of hepatitis B virus (HBV) covalently closed circular DNA (also known as the HBV minichromosome) generates transcriptionally active episomal variants. Chronic HBV infection persists because of a lack of therapies that effectively target the minichromosome, and while the exact fate of the minichromosome after CRISPR-Cas9 editing needs to be eluciated, the findings suggests that designer nuclease approaches could be a promising strategy to treat chronic infectious diseases.

Industry

• U.S.-based Proof Diagnostics has submitted a request for emergency use authorisation to the U.S. FDA, seeking approval for the first CRISPR-based molecular point-of-care test for COVID-19. The test is based upon the CRISPR-based diagnostics method STOPCovid and if authorised, it may be used to deliver accurate, actionable, lab-quality diagnostic results for COVID-19 in as little as 18 minutes.
• Dublin-based ERS Genomics Limited has announced a license agreement with the Central Institute for Experimental Animals (CIEA) in Japan. The non-exclusive licensing agreement grants CIEA access to ERS' CRISPR-Cas9 patent portfolio, which comprises 89 patents held in more than 80 countries. CIEA aims to contribute to medical care and medical science based on the ethical use of animals in modelling of diseases and treatments.
• Earlier this week, Cardea Bio announced the launch of CRISPR QC Inc. as a separate business, using Cardea's CRISPR-chip™ technology for a range of quality control services for CRISPR gene editing. The CRISPR-Chip is an electronic sensor that essentially uses CRISPR-Cas as a ‘DNA search engine’ that can scan genomes and nucleic acid samples with many applications including identification of disease mutations, pathogens, and monitoring the binding efficiencies of Cas variants and guide RNAs during optimisation of CRISPR experiments. You can read more about the CRISPR-Chip in our interview with Cardea Bio CSO Kiana Aran here.
• Verve Therapeutics presented data at the American College of Cardiology 71^st Annual Scientific Session & Expo earlier this week, demonstrating durable and well-tolerated editing of the ANGPTL3 gene in non-human primates (NHPs) for the potential treatment of atherosclerotic cardiovascular disease. The company also revealed that sequential dosing data show administration of PCSK9 base editor followed by ANGPTL3 base editor is well-tolerated in NHPs. Read the press release here.
• BRAIN Biotech AG reported this week that its proprietary CRISPR-Cas genome-editing nucleases BRAIN-Metagenome-Cas (BMC) and BRAIN-Engineered-Cas (BEC) are suitable for genome editing in mammalian cells. This milestone is expected to pave the way for BRAIN’s genome-editing technology to enter very large addressable markets such as animal livestock, cell line development, pharmacology and therapeutics. BEC and BMC are the lead nucleases developed by BRAIN Biotech from a repertoire of around 2,000 untapped Class 2 CRISPR nucleases that the company reported having identified in silico in 2021.
• Earlier this week, ProQR Therapeutics presented data on its proprietary RNA Base Editing Axiomer® Technology, at the 3^rd RNA Editing Summit in Boston. ProQR is leveraging its Axiomer^® RNA base-editing platform to develop transformative RNA therapies for genetic eye diseases, by using the body’s own editing machinery called ADAR to make single nucleotide edits in RNA. The presented data included editing efficiency in various models.
• bluebird bio announed this week that it is initiating a restructuring process to reduce operating expenses by up to $160 million in the next two years, and to advance near-term opportunities to bring potentially curative gene therapies to patients in the U.S. bluebird bio's pipeline contains a number of candidate gene therapies and gene-editing therapies for a range of genetic diseases.

Detection

• Researchers in China and Hong Kong report the development of Microfluidics-Enabled Digital Isothermal Cas13a Assay (MEDICA), a digital droplet-based RPA-Cas13a diagnostic assay format that overcomes the enzymatic incompatibility and macromolecular crowding effect associated with the one-pot assay format. The authors report that MEDICA greatly accelerates the detection reaction and enables relative detection in 10 min and end-point quantification in 25 min and propose that their clinical validation highlights the promise of CRISPR-based isothermal assays for the next generation of nucleic acid quantification methods. The findings were published in Analytical Chemistry earlier this week.

Reviews

• CRISPR Gene Editing of Human Primary NK and T Cells for Cancer Immunotherapy. This review highlights the applications and practicability of CRISPR-Cas9 gene editing and engineering strategies for cancer immunotherapy. The authors also review several approaches to study CRISPR off-target effects.
• CRISPR and Cardiovascular Diseases. This review includes an overview of the various CRISPR-based genome-editing technologies and their impact on cardiovascular basic science research, including animal models, human pluripotent stem cell models, and functional screens. The review also covers emerging therapeutic applications for patients with cardiovascular diseases, focusing on hypercholesterolemia, transthyretin amyloidosis, and Duchenne muscular dystrophy as examples.

Interviews, webinars and podcasts

• CRISPR Pioneer Expects to See Gene-Edited Babies Within 25 Years. Bloomberg News interviewed Nobel Laureate Jennifer Doudna Ph.D. about the progress CRISPR has made and where it can still go.
• Using CRISPR interference (CRISPRi) Viability Screens to Map Long Noncoding RNA Dependencies in Tumor Cells. Free webinar on Thursday, April 21^st, 2022, at 11am EDT (4pm BST/UK). See here for more details and registration.
• CRISPR Screening Roundtable: Stegmaier and Doench. In this free Nature Biotechnology Forum podcast, Kimberly Stegmaier (Harvard Medical School) and John Doench (Broad Institute) speak with Nature Biotechnology senior editor Markus Elsner about the history and latest developments in the field of CRISPR screening.

Conferences

• Registration is open for the 15^th Annual CRISPR Conference, CRISPR 2022, to be held in Cambridge, Massachusetts from June 12^th to June 16^th. View the list of confirmed speakers here, and see here for registration details.

News from CRISPR Medicine News

• For Monday's interview article, we spoke with Eric Kmiec Ph.D. and Kelly Banas Ph.D. of the ChristianaCare Gene Editing Institute, to hear about their new CRISPR-based therapeutic strategy that increases the sensitivity of small cell lung cancer cells to traditional chemotherapy. Read the interview here.
• In Wednesday's clinical trial update, we summarised the two ongoing gene-editing clinical trials for renal cell carcinoma, which is the most common form of kidney cancer found in adults.
• Our sister site CARBON - CRISPR AgroBio News - published another newsletter last Tuesday. Check it out to read about how CRISPR can be used to ensure more nutritious milk from goats. Read the CARBON newsletter here.