Yale Spinout, Couragene, is Revolutionizing In Vivo Gene Editing to Tackle Neurological Diseases
Genetic medicines are a promising new class of therapeutics with the potential to treat a variety of debilitating diseases. However, delivering genetic materials to targeted cells in vivo, or in living organisms, remains a challenge. Couragene, a Yale spinout, was founded to address in vivo gene editing by developing a first-in-class delivery platform with proprietary technology.
Stimuli-responsive Traceless Engineering Platform or STEP, is a platform pioneered by Dr. Jiangbing Zhou, Professor of Neurosurgery and Biomedical Engineering at Yale School of Medicine, which demonstrates potential in overcoming the delivery challenges associated with CRISPR-based genome editing therapy for various diseases.
In an interview with Yale Ventures, Couragene CEO, Dr. Amy Liao, sheds light on the innovative STEP technology pioneered by Zhou. Dr. Liao shares insights into how STEP is addressing critical obstacles and its applications in treating neurodevelopmental diseases.
What are the challenges to translating CRISPR-based therapies in clinical practice?
Amy Liao (AL):
Biological Nature of CRISPR Machinery: The commonly used CRISPR machinery, originating from bacteria, raises concerns about immunogenicity and off-target effects. Persistence within cells over an extended period poses risks.
Blood-Brain Barrier (BBB): The BBB restricts the entry of most agents into the brain through intravenous administration. Direct administration into the cerebrospinal fluid (CSF) overcomes this barrier but presents its own challenges.
Extracellular Space (ECS) Constraints: The narrow width of the ECS in the brain limits the effectiveness of conventional nanoparticles for CRISPR delivery, as they are unsuitable for diffusion in brain tissue.
To tackle these challenges, Dr. Zhou's STEP technology introduces a non-viral delivery platform. This platform allows the efficient delivery of CRISPR machinery in the form of small, transiently acting ribonucleoproteins (RNPs). These STEP-RNPs, approximately 10 nm in size with a negative surface charge, are well-suited for diffusion in brain tissue, overcoming the challenges of drug delivery in the brain.
How is this applied for the treatment of Neurodevelopmental Diseases?
AL: A collaborative team has successfully applied the STEP-RNP-based genome editing approach to treat neurodevelopmental diseases. Specifically, the focus has been on Angelman Syndrome (AS),Prader-Willi Syndrome, and other severe genetic disorders with limited treatment options.
Can you expand applications?
AL: Beyond neurodevelopmental diseases, our team has employed the STEP technology for epigenetic regulation, ribosomal readthrough of premature stop codons, and gene correction, with encouraging preliminary results. Ongoing efforts involve characterizing these systems for various neurodevelopmental and neurodegenerative diseases, as well as diseases in other tissues/organs.
Can you share more about your Impressive 2023 funding milestone?
AL: We are thrilled about the recent achievement of our co-founders being the sole recipients of the UG3/UH3 award by the NIH SCGE program for clinical translation. This substantial grant of ~$40 million over five years will propel the technology through preclinical data generation and towards Phase 1/2 clinical trials.
Can you share more about the team behind Couragene?
The team is led by Dr. Conrad Leung, Couragene CSO, and co-founders Zhou and Dr. Yong-Hui Jiang Professor of Genetics, Neuroscience, and Pediatrics at Yale School of Medicine, providing bioengineering and clinical expertise. Couragene’s R&D team is a group of scientists with extensive experience in construct design, genetic engineering, protein expression, purification, and formulation development.
What advice do you have for Early-Stage Founders?
AL:
Identify True Unmet Needs: Focus on developing solutions for genuine unmet needs in the market.
Build First-in-Class Technologies: Prioritize the development of innovative, first-in-class technologies.
Build a Strong, Complementary Team: Assemble a team with diverse and complementary skillsets to navigate challenges effectively.
Couragene showcases the potential for STEP technology to revolutionize genome medicine and address critical challenges in treating various diseases, particularly in the realm of neurodevelopmental disorders. The impressive funding milestone and the team's expertise position Couragene as a pioneering force in the field of genome editing therapies.