Your Missing Links Are Here (22 January 2021)

Top picks

• Marcello Maresca from AstraZeneca has proposed a universal selection system for precise genome engineering in human cells in Nature Communications. The system is based on editing of the diphtheria toxin (DT) receptor simultaneously with the desired gene modification at a separate locus and subsequent selection of DT resistant cells containing both edits. You can read our interview with Marcello Maresca from last year here.
• Two patients appear to have been cured of ß-thalassemia and sickle cell disease after CRISPR-Cas9 therapy. As part of a clinical trial, researchers deleted the BCL11A gene in patients' stem cells before reinjecting the edited cells that subsequently started the production of fetal haemoglobin. You can read more about the therapies in our comprehensive clinical trial database here and here.

Research

• Reporting in Science, researchers have managed to use CRISPR to track proliferating cancer cells as they metastasise in real-time. Jonathan Weissman from the Whitehead Institute, USA and co-workers engineered lung cancer cells to express Cas9, luciferase, and three pairs of fluorescent genes and gRNAs targeting those genes. When these cells were transplanted to mice lungs and proliferated, new indels were randomly formed in each generation, generating a new fluorescent colour that could be tracked in vivo as metastasis progressed.
• In another attempt to track engineered cells in vivo over time, Canadian researchers have used homology-independent targeted integration (HITI) CRISPR-Cas9 minicircle donors to knock-in multiple reporter genes in mice. The system enables the use of the clinically approved MR reporter gene, Oatp1a1, to localise and track small primary and metastatic tumours that are otherwise not readily detectable.
• American researchers have inhibited CD8+ T-cell exhaustion by deletion of the E3 ubiquitin ligase Cbl-b gene. When cancer cells were transplanted into CD8+ edited mice, tumours grew markedly smaller than in mice with active Cbl-b.
• A new protocol for identifying genome-wide off-target sites of CRISPR RNA–guided nucleases and base editors is described in Nature Protocols. The method uses digested genome sequencing (Digenome-seq) to map in vitro cleavage sites corresponding to on- and off-target sites in cell-free systems.

Industry

• Stocks of three major CRISPR biotech companies - CRISPR Therapeutics, Intellia Therapeutics, and Editas Medicine - have more than doubled in the last few months, reaching a total market value above $23 billion. In a feature article about CRISPR, the business site Barron's gives a comprehensive overview of the gene-editing science and business potential.
• KSQ Therapeutics and Takeda Pharmaceuticals have entered a collaboration worth more than $100 million to develop novel immuno-oncology therapies. The partnership will use KSQ's CRISPRomics discovery platform to identify new targets that modulate T-cells and natural killer (NK) cells.
• China National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for ET-01 developed by EdiGene. ET-01 is an investigational, autologous, ex vivo gene-editing therapy for patients with transfusion-dependent β-thalassemia.
• Base editing company Beam Therapeutics announces $260 million common stock investment from multiple investors. The investment comprises 2,795,700 shares for $93.00 per share, which is approximately 10% below the 5-day volume-weighted average share price.
• The leading gene-editing company Editas Medicine has announced the pricing of an underwritten offering of 3,500,000 shares of its common stock at a public offering price of $66.00 per share. Gross proceeds from the offering are expected to be approximately $231.0 million.
• A three-year-old spun out of Temple University, ExpressCells, has secured its first patent for its "Fast-HDR" gene-editing technology, developed to create advanced cell lines for drug discovery.

Vision and opinion

• The decorated geneticist Eric Lander has been chosen as US president Joe Biden's science adviser and director of the Office of Science and Technology Policy (OSTP). Lander was a crucial figure in the Human Genome Project and is the president and founding director of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.
• Feng Zhang, professor at MIT and a core member of the Broad Institute, has been honoured with the Richard Lounsbery Award for pioneering CRISPR-mediated genome editing. The award is instituted by the National Academy of Sciences and the French Académie des Sciences and is a $75,000 prize given in alternate years.

Review

• A review in Frontiers in Genome Editing takes a close look at targeted gene delivery and discusses the advantages and limitations of different technologies for gene therapy applications. The review is written by Giulia Pavani and Mario Amendola from The Children's Hospital of Philadelphia, USA and Genethon, France, respectively.
• The ongoing efforts to find PAM-free nucleases through natural ortholog mining and protein engineering are addressed in a review in Nature Communications. The review also looks at the potential consequences of fully eliminating PAM recognition.

Heh, huh wow

• India has not yet decided whether to allow CRISPR and other gene-editing techniques to develop better crops, but now several researchers urge the government to approve the technologies. The scientists believe that gene editing can solve problems of decreasing agricultural productivity, loss of arable land, and climate change issues.