CMN Weekly (25 June 2021)
By: Gorm Palmgren - Jun. 25, 2021
- A new alternative to canonical CRISPR-knockout (KO) screens relies on cytosine base editing rather than Cas9-induced DNA double-strand breaks. The new method works by perturbing gene start codons or splice sites or introducing premature termination codons.
- Researchers at Integrated DNA Technologies and Editas Medicine have engineered an enhanced version of AsCas12a, called AsCas12a Ultra. AsCas12a Ultra was designed to have >90% editing efficiency in clinically relevant cells and genes, and it also demonstrated high transgene knock-in efficiencies of up to 60%.
- High editing and homology-directed repair (HDR) efficiencies are obtained with a new delivery system using dendrimer-based lipid nanoparticles (dLNPs). Each dLNP contain Cas9 mRNA, single-guide RNA, and donor DNA, and the weight ratios of the three nucleic acids are systematically optimised to increase efficiency.
- DNAzymes only cut single-stranded DNA, but a new method, PANDA, uses peptide nucleic acid (PNA) to enable nicking or cause double-strand breaks on double-stranded DNA. PANDA is programmable and is both much smaller and has a higher sequence fidelity compared with CRISPR-Cas.
- Editas has started to enrol the first of two planned pediatric cohorts in the Phase 1/2 BRILLIANCE clinical trial of EDIT-101. EDIT-101 is intended to treat people with the blindness disease Leber Congenital Amaurosis (LCA) by editing inherited mutations in the CEP290 gene.
- Sherlock Biosciences and the 221b Foundation will increase the manufacturing capacity of the CRISPR-based COVID-19 diagnostic kit SHERLOCK to 10 million tests per month by year-end. The new agreements will enable manufacturing and global distribution in the U.S., United Arab Emirates, India and Singapore.
- A new company - not yet named - has been established to use CRISPR to develop allogeneic universal CAR T-cell Therapies for immuno-oncology and autoimmune diseases. The new company is launched by a partnership with Blackstone Life Sciences, Intellia Therapeutics and Cellex Cell Professionals and has reached a $250 million financing.
- QIAGEN has launched a series of dedicated CRISPR products for rapid and simplified analysis of gene-editing experiments. The QIAprep& CRISPR Kit and the CRISPR Q-Primer Solutions combine liquid-based sample preparation with downstream PCR detection and Sanger DNA sequencing for characterisation of knock-ins and knock-outs.
- ERASE is a new customised CRISPR lateral flow strip for use in a simple, rapid, ultrasensitive, and highly specific assay for SARS-CoV-2 detection. ERASE can detect down to 1 copy/μL with 90.7% positive predictive agreement and 99.2% negative predictive agreement.
- A review looks at the various methods for using CRISPR-Cas13-based platforms for COVID-19 diagnostics. Detailed and illustrated descriptions of assays like SHERLOCK, SHINE and CREST are given as well as a discussion of challenges and opportunities of point-of-care testing by CRISPR-Cas13 sensors.
- The diversification of the CRISPR toolbox is the subject of a review that explores the broad range of CRISPR applications. Among the applications beyond gene editing, the review mentions controlling gene expression, imaging and diagnostics, and it also takes a look at methods to perform quality control of primary outcomes.
- A review looks at the advantages and disadvantages of various strategies for achieving spatiotemporal control of CRISPR-Cas9 activity. The methods include cell-specific promoters, small-molecule activation and inhibition, bioresponsive delivery carriers, and optical/thermal/ultrasonic/magnetic activation.
- A guest editorial in the CRISPR Journal gives a brief overview of the CRISPR adventures in China. The editorial is part of a special ‘‘CRISPR in China’’ issue of the CRISPR Journal.
- The challenges and opportunities of CRISPR-based molecular biosensing is the subject of a review. The review focuses upon future advancements required to enable rapid, simple, sensitive, specific, multiplexed, amplification-free, and shelf-stable CRISPR-based molecular biosensors.
- "When is it Safe to Edit the Human Germline" is the title of a philosophical study by Janella Baxter, a PhD in philosophy. Baxter sets off with Jiankui He's two CRISPR babies and argues that the recent policy proposals to regulate human germline gene editing are inadequate.
Videos and tidbits
- Get to know the basics of CRISPR in this five-minute video by Scientific American.
- BioPharma Dive has selected eight clinical trials to watch for in 2021. One of them includes using CRISPR, namely Intellia Therapeutics and Vertex's treatment for transthyretin amyloidosis, while another uses gene therapy to treat Huntington's disease.
Heh, huh, wow
- CRISPR-Act3.0 is a new robust CRISPR activation system for simultaneous activation of multiple genes in plants, namely rice, Arabidopsis and tomato. CRISPR-Act3.0 is based on dCas9 and a sgRNA scaffold that includes several MS2 RNA aptamers that can bind multiple VP64-activators. Up to seven genes could be detected simultaneously, and activation was fourfold to sixfold higher than other state-of-the-art systems.
- The first CRISPR-Cas9-based gene drive system has been developed for plants. The method enables the transmission of targeted traits from a single parent in subsequent generations and allows for fast breeding of homozygous F1 crops.
Transfusion Dependent Beta-Thalassaemia, TDT, (NCT04925206)
EdiGene (GuangZhou) Inc.
EdiGene (GuangZhou) Inc.
Multiple myeloma, MM (NCT04960579)
Poseida Therapeutics, Inc.
Poseida Therapeutics, Inc.
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Acute Myeloid Leukemia, AML, (NCT04849910)