CMN Weekly (11 June 2021)
By: Gorm Palmgren - Jun. 11, 2021
Top picks
- American researchers have used CRISPR lineage tracing to reconstruct cancer cell family trees in a mouse model. CRISPR was used to mutagenise synthetically introduced DNA sequences that served as cellular barcodes and were randomly edited in each cell generation. This allowed tracking of 28,000 cancer cells as they spread from the pancreas to other organs and tissues.
- Eric Olson's group at the University of Texas Southwestern Medical Center describes a new CRISPR approach to Duchenne muscular dystrophy (DMD) therapy using SaCas9 from Staphylococcus aureus. This nuclease is smaller than the traditional SpCas9, so a single AAV9 vector suffice to deliver all the necessary editing cargo. The method was used to restore the open reading frame of exon 51 of the DMD gene. We recently reported another strategy used by Olson's group that utilises base editing and prime editing for DMD therapy.
Research
- A paper in Methods in Molecular Biology describes a CRISPR-Cas9-based approach that enables targeted N6-methyladenosine (m6A) addition or removal on endogenous RNA molecules without altering the nucleotide sequence. m6A is a major epitranscriptomic mark exerting crucial diverse roles in RNA metabolisms. The method uses a catalytically inactive Cas9 fused with engineered m6A modification enzymes.
- A new method for the evaluation of gRNA on-target efficiency utilises the LacI-repressor system. A surrogate target site is inserted between the lacI promoter in a construct designed, so cleaving disrupts the repression of luciferase or EGFP expression and leads to a visible signal.
- The crystal structure of the anti-CRISPR protein (Acr) AcrIIA14 has been obtained by Chinese researchers, and it reveals how AcrIIA14 binds to its target Cas9. The results can be used to understand further and utilise this and other Arcs.
- The efficiency of Cas9 and Cas12a to correct the W1282X-CFTR mutation causing cystic fibrosis has been compared in 16HBE cells. Cas9 provided the highest level of correction and was able to restore CTFR function in homozygous-corrected clones fully.
- Significantly truncated or mismatched gRNA spacer sequences can form stronger guide-target bonds than the conventional 18-20bp long spacers. This was shown in cell-free CRISPR activation and CRISPR inhibition experiments. The researchers behind the study propose a thermodynamic model of CRISPR-Cas9 target recognition to explain the results.
Industry
- The company that handles Emmanuelle Charpentier's CRISPR/Cas9 intellectual property, ERS Genomics, have licensed its patent portfolio to genOway. genOway will use the technology to develop pre-clinical disease models in rodents.
- Vertex Pharmaceuticals and CRISPR Therapeutics have presented new data on their joint CRISPR/Cas9 therapy, CTX001, against transfusion-dependent β-thalassemia (TDT) and severe sickle cell disease (SCD). The data address 22 patients with a follow-up of at least three months. According to the press release, the data are impressive in both the consistency and durability of effect.
- Novo Nordisk has entered a research agreement with SNIPR Biome - a leading CRISPR and microbiome biotech company in Copenhagen, Denmark. Under the agreement, Novo Nordisk will evaluate SNIPR Biome's proprietary CRISPR-based CGV Vector™️ technology on an undisclosed target for in situ production of therapeutics in the human microbiome.
COVID-19
- Researchers from Singapore have reported a novel method for the detection of Sars-CoV-2. The method, RADICA, uses a digital CRISPR approach with Cas12a, fluorscent markers and isothermal amplification. It allows for quantification down to 1 copy/µl of SARS-CoV-2 in less than an hour.
- Indian researchers describe a lateral strip paper flow assay that utilises Francisella novicida Cas9 (FnCas9) to detect Sars-CoV-2 within one hour. The assay can discriminate between subtypes of the virus (e.g., N501Y, E484K and T716I) with a sensitivity of 87% and specificity of 97%.
Reviews
- Australian researchers review different ways to reprogram the anti-tumour immune response via CRISPR genetic and epigenetic editing. The authors have studied recently published Cas9-based clinical trial (genetic editing) and dCas9/Cas13-based pre-clinical (epigenetic editing) data. Also evaluated are the potential cancer immunotherapy-specific considerations and barriers surrounding the use of these approaches in the clinic.
- Another review by Chinese researchers focuses on recent CRISPR/Cas9 approaches to construct chimeric antigen receptor T (CAR-T) cells and T cell receptor T (TCR-T) cells. It also reviews the applications of CRISPR/Cas9 in inhibiting immune checkpoint signalling pathways.
- A research highlight in Signal Transduction and Targeted Therapy details the use of high-throughput base editing for precision medicine and drug discovery.
- A methodological review focus on the latest progress in nanoparticle-based delivery of the CRISPR/Cas9 system. The review highlights areas like safety, simplicity and flexibility.
Conferences and courses
- CRISPR Medicine News will host a webinar entitled CRISPR Off-Targets on Wednesday, 23 June. In this webinar, Julia Klermund and Ayal Hendel will talk about two of the newest tools for detecting and characterising unintended on- and off-target events after genome editing. The webinar is free, and you can sign up here.
Tags
CLINICAL TRIALS
IND Enabling
Phase I
Phase II
Phase III
IND Enabling
Phase I
Phase II
Phase III
IND Enabling
Phase I
Phase II
Phase III