Your Missing Links Are Here (23 April 2021)

Top picks

• Beam Therapeutics published new data describing modifications to the traditional base-editing architecture to develop so called next-generation base editors, which can directly and precisely modify the pathogenic mutation in sickle cell disease (SCD). This advance provides hope for the development of autologous base-edited cell therapies for SCD. The findings were published in CRISPR Journal this week.
• Researchers in the US design a new CRISPR strategy ‘Co-opting Regulation Bypass Repair’ (CRBR), which unlike standard CRISPR-Cas - that tends to rely on homology-directed repair proteins that are only present in dividing cells - can be used in dividing and non-dividing cells and tissues. CRBR uses non-homologous end joining to insert a sequence between a mutated gene's promoter and the mutated portion of the gene. This essentially hijacks the promoter to express the newly inserted sequence, which could be a wild-type copy of a disease gene. CRBR has been tested in mice and in human tissue cultures, and proof-of-concept data was published in Molecular Therapy earlier this week.

Industry

• The 221b Foundation, a non-profit organisation established by Sherlock Biosciences has granted licences to Cooper International and United PPE to develop and distribute CRISPR COVID-19 diagnostic kits globally. The newly licenced organisations will use Sherlock’s CRISPR technology and the agreement is expected to lead to increased access in Asia and the Middle East.
• EdiGene, a clinical-stage biotech company focused on gene editing, has secured approximately USD 62 M in Series B financing from a large international group of investors. The funds will be used to advance EdiGene’s pipeline of novel gene-editing therapies into clinics and to scale up its business operation.
• Vertex Pharmaceuticals and CRISPR Therapeuticsamend their collaboration for R&D and commercialisation of CTX001™ in sickle cell disease and beta thalassemia. Vertex will now solely lead the global rollout of CTX001 with financial support from CRISPR Therapeutics in a 60/40% costs/profits split between the two partners, marking a 10 % increase for Vertex compared to the former agreement.
• California-based Allogene Therapeutics has received IND clearance from the U.S. FDA for ALLO-605, the first TurboCAR™ candidate, for the treatment of patients with relapsed or refractory multiple myeloma. You can read more about ALLO-605 and the ALLO-CAR TALEN-based platform in our previous pre-clinical and IND update.
• Allogene Therapeutics was also granted a Regenerative Medicine Advanced Therapy (RMAT) Designation from the FDA this week for another TALEN-engineered CAR candidate ALLO-715 following proof-of-concept data from its ALLO-715 UNIVERSAL trial in heavily pretreated, refractory multiple myeloma patients.
• Vertex and Obsidian Therapeutics form collaboration to leverage Obsidian’s cytoDRiVE® platform technology to discover gene-editing therapies whose activity can be precisely regulated using small molecules with Vertex’s scientific and clinical capabilities in small molecule, cell and genetic therapies to more rapidly bring new gene-editing therapies to the clinic.

Research

• Researchers in Germany succeed in correcting mutations in β-haemoglobinopathies using CRISPR-Cas9 and adeno-associated virus (AAV)-delivered donor templates. The strategy was tested in patient-derived haematopoietic stem and progenitor cell (HSPCs) with promising rates of gene correction and a significant increase in haemoglobin levels. The findings were published in CRISPR Journal this week.
• Chinese researchers show that bubble hairpin single guide RNAs (BH-sgRNAs), which contain a hairpin structure with a bubble region on the 5' end of the guide sequence, can be efficiently applied to both cytosine and adenine base editors and significantly decrease off-target editing without compromising on-target editing efficiency. Their findings were publishd in mBio.
• A team in Australia has developed Generalizable On-target activity ANAlyzer (GOANA), a high-throughput web-based software for determining editing efficiency and cataloguing rare outcomes from next-generation sequencing data. GOANA calculates mutation frequency and outcomes relative to a supplied control sample. The findings were published in CRISPR Journal this week and the tool can be accessed online here.
• Scientists at Editas Medicine have developed CALITAS, a CRISPR-Cas-aware aligner and integrated off-target search algorithm for precise and relevant alignments and identification of candidate off-target sites across a genome. The findings were published in CRISPR Journal and the tool can be accessed here.

COVID-19

• Scientists from India are behind a new publication in Biosensors and Bioelectronics describing FELUDA - FnCas9 Editor Linked Uniform Detection Assay for COVID-19 that utilises a direct Cas9-based enzymatic readout for detecting nucleobase and nucleotide sequences without transcleavage of reporter molecules. FELUDA demonstrates high specificity and sensitivity with results in less than 1 hour and has already completed regulatory validation as a ready-to-use diagnostic kit under the trade name TATA in India.
• A digital warm-start chip-based CRISPR (dWS-CRISPR) assay for sensitive quantitative detection of SARS-CoV-2 in clinical samples has been developed by researchers at University of Connecticut, US. The assays demonstrates sensitivity and precision in clinical swab and saliva samples and could also detect SAR-CoV-2 in heat-treated saliva without RNA isolation. This work was published in Biosensors and Bioelectronics.
• Researchers in Japan have achieved amplification-free SARS-CoV-2 RNA detection with CRISPR-Cas13. The new digital detection platform called SATORI combines CRISPR-Cas13-based RNA detection and microchamber-array technologies and rapidly detects SARS-CoV-2 RNA with high specificity and sensitivity (~5 fM) that was aided by the simulataneous use of multiple different guide RNAs. The findings were recently published in Communications Biology.

Review

• Single-strand template repair: key insights to increase the efficiency of gene editing. A brief review on what is known about the single-strand template DNA repair pathway, and how this knowledge can be used to guide and improve current gene-editing strategies.
• Revisiting cell and gene therapies in Huntington's disease. A review on the cell replacement therapies trialled for Huntington's disease as well as CRISPR-Cas9 editing approaches that have been investigated in animal models and human-derived cells.

Webinars

• 29th April 2021. Free webinar: Precision Genome Editing without Double-Strand Breaks. Speaker: David Liu, PhD. See here for registration.

Interviews and podcasts

• Brown University neuroscientist and Associate Professor Kate O’Connor-Giles discusses how the CRISPR is being deployed to uncover insights about the brain’s function and role in disease.
• Bloomberg Studio 1.0 host Emily Chang sits down with Jennifer Doudna to discuss her work on DNA, CRISPR's breakthroughs in medicine and the ethical concerns they are dealing with.