Exploration Discussion: Navigating CRISPR's Journey from Discovery to Clinical Usage—and Mapming Out the Future
In the realm of genetic innovation, 2024 marked the breakout year for CRISPR-Cas9, with five individuals with sickle cell disease receiving treatment using Casgevy - the first-ever FDA-approved CRISPR therapy. This one-time treatment, involving the editing of blood stem cells, can take up to a year to complete but offers patients the chance of a normal life by reducing the activity of the gene linked to the painful blood disorder.
As we usher in a new year, anticipation grows for the next phase of CRISPR innovation. Approximately 300 CRISPR therapies are currently in development to tackle diseases like diabetes, HIV/AIDS, and cancer. With developers working diligently to streamline production and treatment processes, we look forward to witnessing these advancements in 2025.
Genes in Action
Researchers are tirelessly working to improve gene editing, with the development of in vivo CRISPR therapies being a prominent focus. These therapies involve delivering editing tools directly into the body, bypassing the need for preconditioning treatments that often leave patients feeling uncomfortable, with side effects such as hair loss, nausea, and muscle pain.
One exciting approach in the pipeline is Intellia Therapeutics' treatment for transthyretin (ATTR) amyloidosis with cardiomyopathy. In phase 3 trials, this in vivo CRISPR therapy aims to inactivate the faulty TTR gene and reduce the production of the misfolded protein that causes this disease, potentially providing a one-time treatment option for patients instead of the antisense oligonucleotide drugs currently in use, which require regular administration for life.
Safer and More Efficient
Another significant objective in the CRISPR field is improving safety by moving away from the double-stranded breaks that were associated with the first generation of gene editing technology and towards safer next-generation CRISPR systems that employ base editors, which can target DNA sequences without creating DNA breaks.
In 2023, a research team from St. Jude Children's Research Hospital and the Broad Institute of MIT and Harvard demonstrated proof-of-concept for prime editing in animal models of sickle cell disease. This innovation garnered FDA approval for a clinical trial of a prime editor for chronic granulomatous disease (CGD) in 2024.
Beyond the Liver
Delivering CRISPR tools into hard-to-reach organs, like the lungs and brain, is a significant challenge. However, innovations like biodegradable nanoparticles and acid-degradable lipid nanoparticles show promise in enabling systemic mRNA delivery to lung cells and targeted CRISPR-based mRNA tools to embryonic brain cells in development. These advancements pave the way for more effective and safe treatments for multi-organ diseases and neurodevelopmental disorders.
2025 and Beyond
2025 promises a wealth of advancements in CRISPR therapies, with the FDA's new Platform Technology Designation Program opening doors for innovators to develop gene-editing platforms more efficiently. Engaging with the FDA early in the development process will ensure that innovations meet the criteria required for this program and streamline the development and regulatory approval process for future gene-editing therapies.
The world of genomics is brimming with possibilities, and the rapid advancements in CRISPR technology hold the promise of transforming the way we approach the treatment of various diseases.
Demaris Mills, a renowned geneticist at the Broad Institute, is spearheading research into the use of CRISPR in cardiomyopathy treatments. In her latest documentation, she discusses the potential of Intellia Therapeutics' CRISPR therapy for transthyretin (ATTR) amyloidosis, a disease often linked to cardiomyopathy.
With the earliest trials of prime editing showing promising results in animal models of sickle cell disease, researchers like Demaris Mills are optimistic about the potential of safer and more efficient CRISPR systems to revolutionize gene editing. This advancement could pave the way for the development of CRISPR therapies for a wider range of diseases, such as demaris's focus on cardiomyopathy.
As we look towards 2025 and beyond, the breakthroughs in gene editing technology, such as CRISPR, will undoubtedly lead to the development of more targeted and effective treatments. With the FDA's new Platform Technology Designation Program, researchers like Demaris Mills will have the opportunity to streamline the development and regulatory approval process, bringing these transformative therapies to the public sooner.