CMN Weekly (25 November 2022) - Your Weekly CRISPR Medicine News
Some of the best links we picked up around the internet
By: Gorm Palmgren - Nov. 25, 2022
Top picks
Jennifer Doudna and co-workers have discovered that 0.4% of all phages encode CRISPR systems belonging to all six known CRISPR-Cas types. These include the new Casλ that recognizes double-stranded DNA using a uniquely structured CRISPR RNA (crRNA) and can induce genome editing in mammalian, Arabidopsis, and hexaploid wheat cells. The researchers believe that the viruses use CRISPR to compete with each other and manipulate gene activity in their hosts.
American researchers have developed a method for drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. The technique (PASTE, programmable addition via site-specific targeting elements) uses a CRISPR-Cas9 nickase fused to reverse transcriptase and serine integrase for targeted genomic recruitment and integration of desired payloads. The authors demonstrate the integration of sequences as large as ~36 kilobases at multiple genomic loci across three human cell lines, primary T cells and non-dividing primary human hepatocytes.
Researchers at the Broad Institute have discovered that CRISPR therapies might only sometimes work as intended because people's genomes differ individually and by ancestry. This is particularly true for people of African descent who are more genetically diverse than Europeans or Asians. The researchers mapped ancestry-associated genetic cancer dependencies. They found that most putative associations between ancestry and dependency arose from artefacts related to germline variants present at different frequencies across ancestry groups.
Chinese researchers have explored chemiluminescence resonance energy transfer (CRET) as the readout mode for CRISPR/Cas12a-based biosensing. In contrast to the commonly used fluorescence resonance energy transfer (FRET), CRET does not need external excitation light, which can effectively avoid autofluorescence and photobleaching. As a result, the researchers found that CRET can serve as a rapid, sensitive and straightforward readout mode of CRISPR/Cas12-based biosensing.
Researchers in China have developed a CRISPR-Cas14-based platform for the facile, sensitive and versatile aptasensing of diverse targets. The fluorometric biosensor is named HARRY (highly sensitive aptamer-regulated Cas14 R-loop for bioanalysis) and works opposite most other detection systems: In the presence of the target, ssDNA-target assembly is formed via aptamer interaction, resulting in the inhibition of Cas14a activation, while in the absence of the target, the ssDNA activates Cas14a so trans-cleavage of the fluorescent reporter causes fluorescence enhancement.
Reviews
The genome of β-thalassemia patients can be modified using the CRISPR/Cas9 technique to treat their disease. A review by Iranian researchers highlights the three main approaches that have been taken: 1) increase the expression of γ-globin and production of haemoglobin F, 2) reduction of the α-globin chain to prevent hemolysis of red blood cells by the accumulation of excessive α-globins, and 3) correction of the mutations causing β-thalassemia.