Your Missing Links Are Here (5 February 2021)

Some of the best stuff we picked up around the internet

By: Gorm Palmgren - Feb. 5, 2021

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The majority of pathogenic single-nucleotide variants associated with inherited retinal disease (IRD) can be repaired with base editors. This is the conclusion of a screen of 179 patients and 12,369 alleles implicated in IRD which found that 53% of the pathogenic variants were editable.
According to a paper in Nature Materials, organ-selective mRNA delivery for CRISPR–Cas gene editing has been achieved in spleen, liver and lungs. Successful delivery was obtained using membrane-destabilising ionisable phospholipid nanoparticles.

CRISPR/Cas12a is used in a new ultrasensitive and point-of-care strategy to detect of enzyme activity for T4 PNK, telomerase, or APE1. Detection is visible and based on a lateral flow, fluorescence assay.
A non-editing CRISPRai system for simultaneous activation of thermogenesis (upregulation of UCP1) and increased free fatty acid release from lipid droplets and oxidation (through inhibition of CIDEC) has been developed. The achievement may lead to new opportunities for thermogenesis activation and consequent weight loss.
A telomerase-responsive CRISPR-dCas9-guided nanosystem for precise anti-cancer drug delivery is described in Applied Materials & Interfaces. The method employs drug-loaded nanoparticles that attach to CRISPR-dCas9 and target telomere-repetitive sequences characteristic of cancer cells.
Danish and Iranian researchers have used CRISPR/Cas9 to knockout clinically relevant alloantigens in human primary T cells. The method used electroporation of CRISPR/Cas9 plasmids and managed complete knockout of TCR and CD52 in 7-8% of cells.
An American study has demonstrated proof of principle for a CRISPR-Cas9-based combination gene therapy for HIV. The strategy incorporates a conditional suicide gene and CCR5 knockout (KO) to overcome the limitations of CCR5 KO alone.

According to Zacks Equity Research, Swiss-based CRISPR Therapeutics is expected to deliver a year-over-year decline in earnings on lower revenues when it reports results for the quarter ended December 2020. The company is estimated to report earnings on February 10.
Pairwise, which uses CRISPR technology to enhance fruits and vegetables, announced today that it had raised a $90 million Series B funding round. Included in the company's pipeline are berries with improved shelflife and better-tasting mustard greens.
The CRISPR-patent battle between Broad Institute and Emmanuelle Charpentier (and their respective partners) goes on and gets even more complicated. Read the latest news here.

Chinese researchers present a new CRISPR-Cas13-based transcription amplification method for point-of-care detection of Sars-CoV-2. The method employs light-up RNA aptamers and can detect as little as 82 copies of the virus. Moreover, it discriminates between some mutated variants, including D614G.
Another point-of-care COVID-19 diagnostic system utilises CRISPR Optical Detection of Anisotropy (CODA). The method is based on CRISPR/Cas12a and fluorescent anisotropy, and it can detect down to 3 copy/μL of Sars-CoV-2 RNA within 20 min in a one-pot assay.

In a podcast by Scientific American, they talk about a movie, Son of Monarchs, that brings CRISPR technology to the big screen. In one scene, the main character stands in a crowdy bar and raises his glass to “CRISPR and the genetic revolution.”
Heritable human genome editing pros and cons are the topic for an online discussion on February 26, 2021 at 2 pm GMT. The International Commission on the Clinical Use of Human Germline Genome Editing organises the discussion. The event is free and registration is not required.

In a special issue, the journal Advanced Drug Delivery Reviews brings no less than 16 reviews covering Delivery of Biomacromolecules for Therapeutic Genome Editing.

CRISPR-guided base editing is used as an approach for in situ metabolic reprogramming of industrial microorganisms. The method enables generating large numbers of genetic combinations of diverse ribosome binding sites, 5' untranslated regions, or promoters, without library construction, transformation, and incorporation of DNA donors.