Researchers from multiple institutions in the US report whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing. Using imaging and single-cell genome sequencing of 8-cell stage embryos, the team tracked spontaneous as well as Cas9-induced karyotype aberrations through the first three divisions of embryonic development, and observed the generation of abnormal structures of the nucleus that arose as errors of mitosis. The findings were published in Nature Communications this week, and are in line with earlier reports of whole chromosome loss after CRISPR editing in human embryos (see our interview with Gregorio Alanis-Lobato who uncovered similar findings while working in Kathy Niakan’s group at the Francis Crick Institute, UK, earlier this year).
Clinical news
Allogene Therapeutics Reports FDA Clinical Hold of AlloCAR T Trials Based on a Single Patient Case in ALPHA2 Trial. According to a company press release, the hold was placed after testing in a single patient with low blood counts showed a chromosomal abnormality of unclear clinical significance in ALLO-501A CAR T cells. An investigation is ongoing to understand the finding, and Allogene will host a conference call today at 2:00 p.m. PT/5:00 p.m. ET.
Research from Virginijus Siksnys' lab at Vilnius University in Lithuania found that TnpB of Deinococcus radiodurans mobile genetic element ISDra2 is an RNA-directed nuclease that is guided by RE-derived RNA (reRNA) to cleave DNA next to the 5′ TTGAT transposon associated motif (TAM). Until now, the role of TnpB in transposon mobilisation remained elusive. The team also demonstrated that TnpB could be reprogrammed to cleave DNA target sites in human cells. The findings were published in Nature yesterday.
Using in vivo CRISPR screens, scientists from the US and China have identified that the E3 ligase Cop1 is a modulator of macrophage infiltration in the tumour microenvironment. CRISPR knockout of Cop1 in cancer cells enhanced anti-tumour immunity and strengthened the immune checkpoint blockade (ICB). The authors suggest Cop1 as a target for improving cancer immunotherapy efficacy in triple-negative breast cancer, where ICB benefits are limited. The findings were recently published in Cell.
Researchers at UT Southwestern Medical Center's Touchstone Diabetes Center have successfully used CRISPR gene editing to turn fat cells normally used for storage into energy-burning cells. The discovery was made following transcriptomic analyses following acute cold challenge in DPP4+ PDGFRβ+ adipocyte precursor cells, which revealed changes in the induction of the prothermogenic cytokine, Il33. Doxycycline-inducible CRISPR-mediated deletion of Il33 in PDGFRβ+ cells at the onset of cold exposure led to accrual of fat-burning beige adipocytes. The findings were published recently in Genes & Development.
COVID-19
Scientists in China and Australia have developed a portable RT-LAMP/CRISPR machine for papid COVID-19 screening. The semi-automated device is based on reverse transcription loop-mediated isothermal amplification followed by a CRISPR/Cas12a reaction. The device contains a heater element mounted on a printed circuit board, a cooler fan, a proportional integral derivative controller to control the temperature, and designated areas for 0.2 mL microtubes. The authors report a detection limit of 35 viral copies/microliter, and suggest that their newly developed device has use in crisis centers, mobile laboratories, remote locations, or airports to rapidly diagnose SARS-CoV-2 infections. The findings were published in Biosensors this week.
CRISPR-derived genome editing therapies: progress from bench to bedside. This review discusses the initial development and mechanism of action of CRISPR nucleases and base editors. Factors that should be considered with respect to therapeutic development, including the potential for unintended and off-target edits as well as means to study these outcomes, are also discussed.
World CRISPR Day: The 2nd annual World CRISPR Day (WCD) happens as a virtual even on October 20th, and CRISPR Medicine News will take part as a virtual exhibitor. WCD is organised by Synthego, and the goal is to share, listen, and learn about the latest advances in CRISPR, with presentations from leading scientists in the gene-editing space, a panel discussion featuring the women of CRISPR and more! See here for more information and sign-up details.
The 3rd International Conference on Base Editing – Enzymes and Applications will take place from January 23rd−25th, 2022 in Palm Springs California. Registration is already open, see here for details.