Navigating CRISPR’s Future

December 19, 2023 by Jacqueline Rodriguez

Accomplishments, anticipation, opportunities and challenges

Just like the mantra in real estate is, "Location, location, location," it seems the key to success in CRISPR-based therapies is, "Delivery, delivery, delivery." That was the primary message heard often at the CRISPR 2.0 conference in Boston, which has been a cornerstone for discussing and disseminating innovations and clinical advancement information for CRISPR technology.

Amongst those presenting innovations in the field included Elizabeth (Abby) Stahl, Ph.D., who spoke at Aldevron’s invitation regarding, Genome Editing in the Central Nervous System with Engineered Cas9-RNPs. Her presentation was based on work done at the Innovative Genomics Institute at the University of California, Berkeley, with the guidance of Drs. David Savage and Jennifer Doudna, where Stahl was a postdoctoral fellow.

Discussions were also driven by the groundbreaking approval in the United Kingdom of the first CRISPR-based therapy for sickle cell disease and beta-thalessemia, called Casgevy. The US Food and Drug Administration also approved Casgevy on December 8, after the event.

The news about the UK approval gave event attendees and presenters a solid starting point to delve further into the challenges and opportunities that lie ahead for making CRISPR therapies more accessible and effective. Based on the speaker discussions and the latest development news, the event focus was on several categories.

Regulatory Evolution and Quality Control
There has been a significant shift in the regulatory landscape, with CRISPR now being regulated as a drug substance. This change reflects a deeper understanding and respect for the technology's potential and risks. Experts emphasized the critical role of analytics in this space, with a unanimous agreement that quality control (QC) is paramount. These discussions underscored the complexities in phenotypic analysis in clinical trials, the need for sensitive and validated QC methods, and the challenges posed by species-specific targets.

Breakthroughs in Delivery Mechanisms
A key focus was on the delivery mechanisms of CRISPR therapies, such as those Stahl discussed in her talk. Ribonucleoprotein (RNP) complexes* were noted for their potential due to their small size, particularly in ex vivo applications and in treating brain conditions. Lipid nanoparticles (LNPs) were discussed as an efficient in vivo delivery method, offering an alternative to viral vectors. These advancements underscore the field's ongoing quest to overcome delivery challenges. My colleague Dave Yoder will expand on this topic in an upcoming post.

Bridging the Gap Between Academia and Clinical Applications
There were also focused discussions to shed light on the disconnect between academic research and clinical data, particularly in chemistry, manufacturing, and controls (CMC). This gap represents a crucial area for future collaboration and innovation.

Priorities in CAR-T Therapies and Safety Concerns
For CAR-T therapies, the focus remains on enhancing efficacy through checkpoint disruption, immune cloaking, and cytokine support. However, concerns about off-target effects (OTE) and immunogenicity continue to be a major discussion point, emphasizing the need for precision and safety in developing these therapies.

Innovations in Gene Editing Techniques
Exciting developments in base editing and prime editing were highlighted as these techniques represent a significant advancement by avoiding double-stranded breaks, reducing the risk of unwanted genetic changes, and improving efficiency and specificity.

As shown with the approval of Casgevy, there is a sense of excitement and anticipation for the future of CRISPR-based therapies. Regulators and the industry are at a critical juncture, shaping the trajectory of ongoing developments. Developments in gene editing have been long in development, but it appears the industry is now on the cusp of some amazing new discoveries and therapies, giving hope that the next decade promises even more groundbreaking developments.

• Visit our CRISPR solutions web page
• View our webinar, CRISPR Genome Editing Solutions from Discovery to Clinic
• View our webinar, CRISPR Cures 2033
• Want to know more about this topic? Contact Jacqueline Rodriguez
• Have an idea for a topic? Let us know!

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