CMN Weekly (9 September 2022) - Your Weekly CRISPR Medicine News

Top picks

• New research findings from Penn State University in the U.S. reveal a new approach to Cas9-based genome editing in human pluripotent stem cells that is reported to more than double stem cell editing efficiency while reducing off-target activity. The findings were published in Cell Reports Methods earlier this week, describing the team's efforts to develop non-integrating and efficient modified mRNA (modRNA)-based CRISPR systems (Cas9 or base editor) that can be employed to achieve robust gene knockouts in human embryonic stem cells and induced pluripotent stem cells to overcome the challenges faced by plasmid-based CRISPR delivery systems.
• How CRISPR Is Changing Cancer Research and Treatment. This overview by the National Cancer Institute (U.S.) presents CRISPR-Cas9 as a gene-editing tool and discusses its merits and limitations in the context of therapeutic applications, before highlighting the first CRISPR clinical trial for cancer, which was launched at the University of Pennsylvania in 2019.

Research

• In an article published in Scientific Reports this week, scientists in Columbia report the delivery and assessment of a CRISPR/nCas9-based genome-editing system on various in vitro models of mucopolysaccharidoses IV A (MPS IVA), assisted by magnetite-based nanoparticles. MPS IVA is a lysosomal disorder caused by mutations in the GALNS gene, which leads to a damaging buildup of glycosaminoglycans in the lysosomes. The team found that CRISPR/nCas9 treatment - which was delivered via a novel non-viral vector based on magnetoliposomes - led to an increase in enzyme activity between 5 and 88% of wild-type levels, as well as a reduction in glycosaminoglycan accumulation, lysosomal mass, and mitochondrial-dependent oxidative stress, in a mutation-dependent manner. The findings point towards CRISPR/nCas9 as a new treatment strategy for MPS IVA.

Industry

• Bristol Myers Squibb-backed Arsenal Bio has secured $220M in series B funding for non-viral gene-edited cell therapies for cancer, bringing its total funding to date to $300 million in less than three years. The new funding will finance more staff and advance the company’s early programmes toward the clinic, which are led by Arsenal’s lead asset AB-1015, an ovarian cancer candidate for which FDA Investigational New Drug (IND) clearance and first patient dosing are targeted for later this year.
• Intellia Therapeutics has announced an upcoming investor event to present interim clinical data from ongoing first-in-human studies of NTLA-2002 and NTLA-2001 on September 16^th, 2022. The updates will include a review of the first clinical data from a Phase 1/2 Study of NTLA-2002 for hereditary angioedema (HAE), to be presented at the 2022 Bradykinin Symposium, as well as interim safety and serum TTR reduction data from the cardiomyopathy arm of the Phase 1 study of NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis. Read more about NTLA-2002 and NTLA-2001 in previous clinical updates here and here.
• Wageningen University & Research (WUR, Netherlands), together with spin-off Scope Biosciences, has received a grant of €150,000 from the European Research Council. The grant is intended to further research and enhance their diagnostic technology ScopeDx, which is based on CRISPR-Cas technology, and is able to quickly and accurately recognise viral or bacterial RNA.

Reviews

• Diverse Approaches to Gene Therapy of Sickle Cell Disease. This review discusses the various gene therapy-based approaches to treating sickle cell disease and highlights the progress that is being made in ongoing clinical trials.
• Stimuli-responsive delivery strategies for controllable gene editing in tumor therapeutics. This review summarises the synthesis of stimuli-responsive nanocarriers by designing key chemical structures to achieve controllable release of gene-editing reagents. Nanocarriers controlled by biochemical or physical signals are also discussed, as well as potential challenges and prospects for existing nanocarriers.
• Approaches to Gene Modulation Therapy for ALS. In this review, authors in the U.S. discuss the latest clinical and pre-clinical advances in gene modulation approaches for amyotrophic lateral sclerosis (ALS), including gene silencing, gene correction, and gene augmentation. According to the authors, these techniques have the potential to positively impact the direction of future research trials and transform ALS treatments for this grave disease.
• Advanced molecular therapies for neurological diseases: focus on stroke, alzheimer's disease, and parkinson's disease. This review explores advances within emerging therapies, such as gene therapy (gene editing and gene silencing) and stem cell therapies, to treat or even cure neurological diseases. Strategies involving CRISPR-Cas, gene silencing using siRNA, and stem cell therapy aims are discussed.
• Genome editing for primary immunodeficiencies: A therapeutic perspective on Wiskott-Aldrich syndrome. In this review, scientists at Great Ormond Street Institute of Child Health (London, UK) discuss the progress made towards the development of gene editing-based therapeutic strategies for primary immunodeficiencies with a special focus on Wiskott - Aldrich syndrome and outline their main challenges as well as future directions with respect to already established treatments.
• Genetic treatment for autosomal dominant inherited retinal dystrophies: approaches, challenges and targeted genotypes. This review discusses zinc fingers, RNA interference, antisense oligonucleotide therapy, translational read-through therapy, and gene editing by CRISPR/Cas as some of the dominanting strategies that are currently under investigation for the treatment of inherited retinal dystrophies.

Conferences

• CRISPR and Beyond: Perturbations at Scale to Understand Genomes. This conference will explore methods to modulate the genome at scale, and will be held from 28^th–30^th September 2022 at Wellcome Genome Campus, UK and virtually. See here for more information and link to registration.
• 5^th International Conference on CRISPR Technologies. This conference will take place between 31^st October and 2^nd November 2022 at UC Berkeley (California). The event will bring together investigators focused on enzymes and technologies, predominantly CRISPR-based systems, but also other promising systems and approaches, to discuss advances in the field and ways to harness genome engineering for beneficial purposes. Abstract admission open, see here for details.
• CRISPR 2.0 Summit. A virtual conference running between November 16^th-18^th, 2021. Registration is open, see here for more information.

News from CRISPR Medicine News

• On Monday, we published an interview with Cecilia Jimenez-Mallebrera PhD. She is Director of the Laboratory of Translational Research in Children’s Neuromuscular Diseases at the Institut de Recerca Sant Joan de Déu in Spain, and she has been studying neuromuscular diseases for several decades, specialising in ultra-rare congenital muscular dystrophies in children. Recent research findings by her team provides new hope for these diseases, demonstrating the power of CRISPR-Cas9 to silence a dominant negative mutation in patient fibroblasts. Read the interview here.