Your Missing Links Are Here (30 April 2021)

Top picks

• iPS cells from a patient with adult progeria Werner syndrome have been obtained, and the disease-causing mutation in the WRN-gene has been corrected by CRISPR-Cas9. These iPSC lines would be a valuable resource for deciphering the pathogenesis of Werner syndrome and might lead the way for a therapy.
• The severe metabolic liver disease hereditary tyrosinemia type I has been corrected in a mouse model using CRISPR. The American researchers used AAV-delivery for the targeted insertion of a promoterless fumarylacetoacetate hydrolase (FAH) gene into the Apoa1 locus to achieve the feat.

Research

• An international team of researchers demonstrates successful genome editing in primary human islets using CRISPR-Cas9. The team managed to edit several genes and non-coding DNAs targeting type 2 diabetes risk variants and thereby altering various islet β-cell regulators.
• Ligand-activation of guide RNA to control CRISPR/Cas9 function has been obtained by integrating of the theophylline aptamer into protein-unrecognized regions of guide RNA. The method opens a new window towards conditional control of CRISPR-Cas9 function.
• Iranian researchers have developed a colourimetric aptasensor to detect as little as 0.05 ng/L aflatoxin M1 in spiked milk samples. The aptasensor is based on the catalytic activity of gold nanoparticles, CRISPR-Cas12a and rolling circle amplification.

Industry

• CRISPR Therapeutics is to receive a hefty $900m payment in a reworked deal with Vertex dating back to 2015. In the new deal, CRISPR Therapeutics will have to pay 40% of its development expenses (up from 0%) but receives the huge upfront payment with a further $200 million due upon the first regulatory approval of its CTX001 therapy for β-thalassemia and severe sickle cell disease.
• CRISPR Therapeutics and Vertex Pharmaceuticals has been granted Priority Medicines (PRIME) designation to CTX001 by the European Medicines Agency (EMA). PRIME is a regulatory mechanism that provides early and proactive support to developers of promising medicines to optimize development plans and speed up evaluations so these medicines can reach patients faster.
• Staying with CRISPR Therapeutics will present new information about its ongoing Phase 1 CARBON trial at the virtual American Society of Clinical Oncology Annual Meeting (ASCO) from 4 to 8 June 2021. The trial studies the safety and efficacy of the CTX110 therapy for relapsed or refractory (R/R) B-cell malignancies. CRISPR Therapeutics has also presented business updates and first quarter 2021 financial reports.
• Allogene Therapeutics willl present data from its Anti-CD19 AlloCAR T™ therapy program in relapsed/refractory non-Hodgkin lymphoma at the American Society of Clinical Oncology (ASCO) from 4 to 8 June 2021.
• Twist Bioscience Corporation and Vivlion GmbH have announced cooperation for generating gRNA libraries for CRISPR applications. The partnership will use Vivlion's proprietary 3Cs technology that bypasses standard cloning methods such as PCR amplification for direct conversion of Twist's high-quality Oligo Pools into uniform gRNA libraries.

Events at the Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), 11 to 14 May 2021

• Beam Therapeutics will contribute with oral and poster presentations.
• Intellia Therapeutics will contribute with presentations.
• Fate Therapeutics will contribute with four presentations.
• Precision BioSciences will contribute with a poster presentation.
• Sangamo Therapeutics will contribute with presentations.

People and opinion

• Pioneer in CRISPR-Cas9 development David Liu has been elected a new member of the National Academy of Sciences in the US. Liu is among 119 other new members that now bring the Academy's total number of members up to 2,641.
• An easy-to-understand piece sheds light on the complex legal battle for ownership of CRISPR patents. The battle not only involves the three central players - Jennifer Doudna, Emmanuelle Charpentier and Feng Zhang - but also Vilnius University, DowDuPont, MilliporeSigma and Cellectis that all own CRISPR patents.

Reviews

• A review in Trends of Genetics looks into how DNA double-strand breaks are repaired by, e.g., microhomology-mediated end joining (MMEJ) or homology-directed repair (HDR) after CRISPR-Cas9 cutting. The review dives into the involvement of several key factors, including the cell cycle, target site sequence and chromatin structure, and the identity of the donor DNA template.
• The use of CRISPR genetic and epigenetic editing of immune cells can reprogram the anti-tumour immune response. A review in Molecular Therapy - Methods & Clinical Development examine the possibilities by, e.g., expressing synthetic immune receptors and inhibiting the expression of immune checkpoints.
• A review in Bio Integration takes a look at the milestones of CRISPR/Cas technologies that advanced the field of diagnostics and gene therapy. The Korean authors also discuss the strength and significant challenges of the CRISPR/Cas technology for its future clinical usage in diagnosis and gene therapy.

COVID-19

• A new CRISPR-Cas9-based method can distinguish SARS-CoV-2 and its D614G variant with single-base resolution in patient samples. The technique is called LEOPARD and is based on the observation that tracrRNAs can hybridise to cellular RNAs. This results in the formation of "noncanonical" crRNAs capable of guiding DNA targeting by Cas9.
• Japanese researchers report a new platform, SATORI, to detect SARS-CoV-2 N-gene RNA at ~5 fM levels. The method combines CRISPR-Cas13-based RNA detection and microchamber-array technologies.

Conferences and webinars

• The Synthetic Biology Biopharma Conference 2021 will focus on how 2020 transformed the Biopharma Industry and how technologies and diagnostic capabilities continue to accelerate drug discovery. The online conference will take place 26-27 May 2021.