Your missing links are here (30 October 2020)

Top Pick

• A detailed analysis of unexpected, undesirable outcomes after CRISPR editing of genes in human embryos shows that CRISPR/Cas9 is not yet ready for clinical use to correct mutations at this stage of human development. The researchers from Columbia University found that in human embryonic cells, a single break in the DNA very frequently leads to the loss of an entire chromosome or sometimes a large segment of that chromosome.

Research

• CRISPR-Cas9 leads to double-strand breaks that are either repaired by homology-directed repair (HDR) leading to precise repair or by non-homologous end joining (NHEJ) leading to indels. A German study shows that CRISPR performed while co-expressing Ubiquitin binding domain proteins reduces NHEJ and shifts the HDR/NHEJ balance up to 6-fold.
• In another approach to increase the frequency of HDR, Japanese researchers have fused anti-CRISPR proteins to a protein that is degraded specifically in S and G2 cell cycle phases when HDR is dominant. Co-expression of this construct and Cas9 increased the frequency of HDR and also suppressed off-targets effects.
• Chinese researchers have identified a potential gene-editing target for the treatment of cardiomyocyte hypertrophy (increased cardiac muscle mass) in early childhood. The gene Myh7 was identified in a mouse model using CASAAV - a CRISPR based platform for rapid dissection of gene function in vivo - and its inhibition led to a reversal of the disease.
• Prime editing is an effective means for correcting a mutation in the ATP7B gene that causes Wilson disease in which excess copper builds up in the body. Dutch researchers demonstrated this in a patient-derived disease model using 3D grown organoids of liver cells.
• Another CRISPR-based genetic screening tool is targeted for human cerebral organoids. German researchers have developed a technique called CRISPR-LICHT that combines CRISPR-Cas9 and a dual-barcoding system so hundreds of genes can be screened in parallel. As the name implies, results show up in coloured immunoflourescence images.

Delivery

• Electroporation is sometimes used for delivering gene-editing machinery to target cells, but most commercial electroporation machimes are not suited for large-scale, automated use. Now, American researchers have developed a microfluidic continuous-flow electrotransfection device that was demonstrated to deliver mRNA into 500 million T-cells at a rate of 20 million cells/min.

Industry

• Bayer has acquired the AskBio that specialises in AAV vector delivery systems, capsid development, and clinical-stage manufacturing. The acquisition is expected to broaden Bayer's innovation base in cell and gene therapy.
• CRISPR Therapeuticsstocks fell 3.5% after disclosure of disappointing third-quarter results. A net profit of $138.4 million from the same quarter last year has turned into a loss of $92.6 million this quarter. The main reason for the fall is that CRISPR Therapeutics last year received development funds from longtime partner Vertex.
• Biotechnology company Aldevron - that among other things produce CRISPR Ribonucleoproteins (RNPs) for DNA-free delivery of CRISPR/Cas systems - has received a premier technology business award by the Technology Council of North Dakota. The prize was given for Aldevron's achievements and contributions to the biotech industry through innovation and expertise.
• CRISPR technology market size is estimated to significant annual growth of 24% by 2030. Increased funding from private and government organisations is considered a key factor for growth.
• Mammoth Biosciencessigns agreements with MilliporeSigma to scale manufacturing and with Hamilton Company to market a turnkey solution to help CLIA laboratories rapidly add testing capacity. The test leverages Mammoth’s DETECTR BOOST™ platform and will provide a sample-to-answer turnkey solution for commercial laboratories to enable a multi-fold increase in testing capacity.

Visions and Opinion

• Rodolphe Barrangou from North Carolina State University - who first revealed CRISPR as a bacterial adaptive defence system in 2007 - explains in an interview with NutraIngredients-USA that he expects CRISPR is going to reshape the future of probiotic genomes. Barrangou will speak about his vision at the IPA World Congress + Probiota Americas Digital Summit 2020 in November.

Clinical Trials

• Rubius Therapeutics has presented preclinical data for RTX-321, a red cell therapeutic oncology product candidate for HPV-positive cancers. The data demonstrate that RTX-321 has a dual mechanism of action by not only functioning as an antigen-presenting cell to boost HPV 16 antigen-specific T cell responses but also promoting broad immune system stimulation of both innate and adaptive immunity.

COVID-19

• A genome-scale, loss-of-function CRISPR screen to systematically knock out all genes in the human genome has revealed individual genes and gene regulatory networks that are required by SARS-CoV-2 and that confer resistance to viral infection when suppressed. One crucial finding was that loss of RAB7A - a gene involved in endocytosis - prevents viral entry by sequestering ACE2 receptors inside cells.
• Another genome-wide CRISPR screen has unveiled genes that affect the import, export, and metabolism of pervasively used antiviral drugs in the treatment of coronavirus disease (COVID-19). Among the findings was that the drug-transporting gene ABCC1 was pivotal in exporting and inactivating remdesivir.

Beyond Medicine

• You already know cane sugar and beet sugar - but here comes rice sugar. Chinese researchers knocked-out the GCS1 gene in rice using CRISPR technology and found that the resulting rice plants had ovules (seed progenitors) containing 10-20% high-quality sucrose. The researchers suggest that this can pave the way for developing new sugar-producing crops suitable for diverse ecological zones.
• A 100% female-to-male sex conversion in Drosophila fruitflies has been achieved using CRISPR/Cas9 HDR-induced point mutations in the sex determination gene tra2. The German researchers suggest that their achievement can eventually be used in eradication of insect pests like mosquitos.