Your Missing Links Are Here (19 February 2021)

Top picks

• Bluebird bio has halted a clinical trial after two patients developed leukaemia-like cancer. The trial used gene therapy to treat sickle cell disease by introducing a functional gene - and thus, it is not a kind of gene editing. The cancer is not necessarily linked to the gene therapy, but might have been caused by the chemotherapy treatment used to prepare patients for the ex vivo treated blood stem cells.
• An international research team led by Rory Johnson from University College Dublin, Ireland, has significantly enhanced the efficiency of CRISPR-Cas9 deletion. The enhancement is obtained by repressing the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) that controls an early step in nonhomologous end-joining (NHEJ). The new method works across diverse cell lines, gene delivery methods, commercial inhibitors, and guide RNAs.

Research

• Swiss researchers have developed an optimized workflow for CRISPR-Cas9 deletion of surface and intracellular factors in primary human T lymphocytes. The approach may be beneficial for the study and treatment of a range of infectious and chronic diseases.
• Chinese researchers have developed an efficient method for the delivery of CRISPR-Cas9 to induce germline mutagenesis in mosquitoes. The method uses microinjection of ribonucleoprotein complex into the ovary or hemolymph, and its efficacy was tested by knocking-out the eye pigmentation kmo gene. The finding can facilitate ongoing efforts to control the disease vector.
• Other Chinese researchers have demonstrated a method that uses paired Cas9 nickases to generate iPSC lines with different gene dosages of duplicated genes. The technique enabled the generation of iPSC lines with monoallelic, biallelic, or triallelic knock-out of the amyloid precursor protein (APP) gene in Alzheimer's patients carrying three copies of the gene. The approach opens up for the development of new clinical therapeutics for dementia.
• A promising method to inhibit the progression of lung adenocarcinoma in vivo has been shown in xenografts. The results were achieved by CRISPR interference (CRISPRi) targeting the novel, noncoding oncogenic driver FAM83H‐AS1.
• David Liu and colleagues have developed new software, PrimeDesign, for the rapid and simplified design of prime editing guide RNAs. The authors used the software to construct a comprehensive and searchable database that includes candidate prime editing guide RNA (pegRNA) and nicking sgRNA (ngRNA) combinations for installing or correcting >68,500 pathogenic human genetic variants.
• A novel, highly specific detection system for multidrug-resistant Acinetobacter baumannii uses multiplex PCR followed by CRISPR-Cas12a detection. The method both enhance the detection limit and the specificity to recognize specific genes in bacteria.

Covid-19

• A study has compared the efficacy of a CRISPR-based screening method for Sars-CoV-2 with the gold standard RT-qPCR method. The study included 1,808 asymptomatic college students, who self-collected oropharyngeal swabs. Results showed that the Cas13-based method (CREST) reached results almost identical to the PCR-based method.

Industry

• Excision BioTherapeutics announces the completion of a $60 million financing to advance CRISPR-based HIV-treatment. As a result of the funding, the Company's lead candidate EBT-101, which targets and deactivates viral genes, will go into a phase I/II clinical trial in patients with chronic HIV infection.
• In an interview with Endpoint News, gene editing expert Charlie Albright explains why he left Editas for a new role as CSO of upstart biotech gene therapy company Affinia. After four weeks in the new job, Albright believes Affinia can address some of the fundamental issues in AAV gene therapy.
• A license agreement has granted the contract research organization ZeClinics access to ERS Genomics's CRISPR/Cas9 patent portfolio to knock-out genes in its zebrafish disease models. ERS Genomics holds the intellectual property of Nobel Laureate Emmanuelle Charpentier.
• As expected, CRISPR Therapeutics has announced substantial losses of $107.0 million for the fourth quarter of 2020 and $348.9 million for the year ended December 31, 2020. The decrease is primarily attributable to the sale of certain licenses under the Company's collaboration with Vertex during 2019.
• Cytovia Therapeutics and Cellecti have announced a strategic research and development collaboration to develop TALEN gene-edited induced pluripotent stem cells (iPSCs) natural killer (NK) and chimeric antigen receptor (CAR)-NK cells. The partnership's financial terms include up to $760 million of development, regulatory, and sales milestones from Cytovia to Cellectis for the first 5 TALEN gene-edited iPSC-derived NK products.
• According to a report published by Fior Markets, the global genome editing market is expected to grow from USD 5.37 billion in 2020 to USD 17.36 billion by 2028, at a CAGR of 15.8% during the forecast period 2021-2028. The growth is driven by increasing clinical application fields and rising production of GM crops.
• CRISPR stocks have soared 4-5 times in the last few years, so the question now is: should you buy or should you sell? Forbes gives you some pieces of advice.
• Intellia Therapeutics will present its fourth quarter and full-year 2020 financial results and operational highlights in a conference call on 25 February.
• AbbVie and Caribou Biosciences have signed an agreement to develop novel off-the-shelf chimeric antigen receptor (CAR)-T therapies. Caribou will receive a $40 million upfront payment in return for AbbVie gaining access to its next-generation Cas12a CRISPR hybrid RNA-DNA (chRDNA) platform.

Vision and opinion

• An opinion piece in Scientific American addresses the consequences of using CRISPR and other gene-editing techniques to "reduce human diversity and increase social inequality by editing out the kinds of people that [...] are understood as having bad genes."The piece is written by Sandy Sufian, associate professor of health humanities and history at UIC School of Medicine, and Rosemarie Garland-Thomson, professor of English at Emory University, who were both born with severe genetic conditions.
• Carl June from the University of Pennsylvania, US, is among this year's Dan David Prize laureates that were announced this week. June is a pioneer in CRISPR-based cancer therapies, and CRISPR Medicine News interviewed him last year. The seven laureates share $3 million in the three categories: History of Health and Medicine, Public Health, and Molecular Medicine.
• The Financial Times has reviewed two books, The Code Breaker by Walter Isaacson and Crispr People by Henry Greely, seeking to start the public debate on whether we should alter our genomes. Isaacson focuses on the battle between Jennifer Doudna and Feng Zhang over who gets credit for CRISPR, while Greely sets out to unravel the story of He Jiankui and his CRISPR-babies. Greely's book is also reviewed in Sceince.

Meetings, webinars and podcasts

• A webinar arranged by Illumina and 10x Genomics will address the advances in single-cell CRISPR. Researchers Shiqi 'Russell' Xie from Genentech and Lea Starita from the University of Washington will discuss the matter on 26 February.
• The Secret Ingredient in Your Gene Therapy Success Recipe is the title of a podcast by Cell Culture Dish. The podcast features host Brandy Sargant interviewing Ratish Krishnan from MilliporeSigma to talk about the tremendous promise gene therapies have for changing the healthcare paradigm and challenges in manufacturing and solutions.

Reviews

• CRISPR-Cas-mediated platforms to tackle sensorineural hearing loss is the subject of a new review. The review summarises new findings on gene editing of human induced pluripotent stem cells (hiPSCs) to alter genes from hair cells and spiral ganglion neurons.

Heh, huh, wow

• Research work to produce Ghana's first gene-edited crop with increased vitamin A content has begun at the University of Cape Coast. The project will use CRISPR to knock out the production of an enzyme that converts beta carotene - a precursor of vitamin A - into other products. Sweet potato is very resilient, has a high yield and is adaptable to many environmental conditions expected from climate change.