CMN Weekly (8 October 2021)

Some of the best links we picked up around the internet

By: Karen O'Hanlon Cohrt - Oct. 8, 2021

Top picks

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.
  • Intellia Therapeutics receives authorisation to initiate Phase 1/2 clinical trial of NTLA-2002 for the treatment of hereditary angioedema (HAE), a rare disorder that is characterised by recurrent episodes of severe swelling. NTLA-2002 is the first single-dose genome editing therapeutic candidate for HAE to enter a clinical study, and the company expects to begin enrolment before the year ends.

Research

  • 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.

Reviews

Conferences

  • The Society for Immunotherapy of Cancer (SITC) annual meeting takes place from November 10th to November 14th this year. This year's meeting will be held virtually as well as physically with pre-clinical presentations expected from Beam Therapeutics, Poseida Therapeutics, Fate Therapeutics, Editas Medicine, CRISPR Therapeutics, and Graphite Bio. See SITC website for more details.
  • 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.

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Acute Myeloid Leukemia, AML, (NCT05066165)
Sponsors:
Intellia Therapeutics
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IND Enabling
Phase I
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IND Enabling
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CAR T for CD19+ hematological cancers, (NCT05037669)
Sponsors:
University of Pennsylvania
Indicator
IND Enabling
Phase I
Phase II
Phase III
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