Expectations are high for this year in the CRISPR research community, as the world’s first therapy based on this technique nears a potential FDA approval.
CRlSPR gene editing has long attracted attention in the research community, the media, and the wider public. This peaked in 2020 when the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to two leading CRISPR researchers, Jennifer Doudna and Emmanuelle Charpentier. However, the field has also faced controversies. In December 2019, He Jiankui, a Chinese scientist, was sentenced to a three-year imprisonment after news broke of him using CRISPR technology to edit human embryos that led to the birth of three babies. Jiankui was reported to have been released in 2022.
Additionally, a legal battle between Feng Zhang and scientists from the Broad Institute and Harvard, and Jennifer Doudna from the University of California, over who invented the technique and patents linked to it has ensued in recent years. In February 2022, the US Patent and Trademark Office declared that the Broad Institute could keep its patents for CRISPR-Cas9 editing in eukaryotes and, thus, humans. Nevertheless, questions surrounding the ultimate ownership of the technology remain, as patent offices in other countries have reached different conclusions.
While some gene therapies work by adding functional copies of modified genes to correct a defect, gene editing via CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, can target and modify specific DNA sequences. A guide RNA leads the Cas9 enzyme to a targeted DNA sequence, which can be edited for the desired change. Importantly, CRISPR editing is more accessible than other methods, making CRISPR-based research easier and more affordable.
Still, no therapies that use this approach are approved yet. But this could soon change. At the 2022 Annual Meeting of the American Society of Hematology (ASH), some of the most advanced CRISPR-based treatments in development for the treatment of blood disorders were showcased. Of these, the gene therapy made by CRISPR Therapeutics and Vertex Pharmaceuticals, exagamglogene autotemcel–also known as exa-cel, is the closest to a potential approval. Both companies plan to complete the therapy’s BLA submission for the treatment of sickle cell disease (SCD) and transfusion dependent beta thalassemia (TDT) by the end of Q1 2023, following positive data.
Clinical successes like exa-cel are bringing the potential of a CRISPR-based treatment closer to patients. “The momentum is real. 2021 was great, and 2022 was even better,” says Rodolphe Barrangou, PhD, Todd R. Klaenhammer Distinguished Professor in probiotics research at North Carolina State University, Raleigh. Barrangou is the co-founder of Cambridge, Massachusetts-based Intellia Therapeutics, a developer of CRISPR gene therapies, where he remains a member of the scientific board. In 2023, it will be important to continue testing such treatments in Phase I trials in diverse indications and patients for the next generation of gene therapies, he says.
Although the first approval will be a milestone for CRISPR therapies, some experts interviewed by this news service emphasised that the industry is making progress even outside of potential approvals and late-stage trials. This year will be critical for the establishment of regulatory precedents in CRISPR gene editing, which some experts say is essential for the field’s further development.
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