Casebia Therapeutics, an innovative gene editing company discovering and developing curative treatments for genetic diseases, today presented new research on an innovative gene editing approach to manage production of Factor VIII (FVIII) for therapy of hemophilia A. As part of a presentation during the International Society on Thrombosis and Haemostasis (ISTH) 2019 Congress, Principal Scientist Alan Brooks highlighted findings that stable, titratable expression of FVIII in mice using CRISPR/Cas9 gene editing was demonstrated.
“Our scientific team, led by Alan Brooks, Ph.D., have achieved a notable and potentially impactful advance towards a curative treatment for patients with hemophilia A – hemophilia affects an estimated 400,000 people worldwide with a majority having hemophilia A,” said Jim Burns, Ph.D., President and CEO of Casebia. “While acknowledging that early-stage results in animal models do not always translate into successful human treatments, we are extremely encouraged by the results.”
As detailed in the oral presentation, entitled Therapeutic Levels of FVIII Generated by CRISPR/Cas9-mediated in vivo Genome Editing in Hemophilia A Mice, the Casebia team was able to achieve expression of therapeutic levels of FVIII using a unique two-stage gene editing process.
Hemophilic mice were first treated with an adeno-associated virus (AAV) carrying a human FVIII coding sequence – the instructions for synthesizing FVIII, the protein necessary for normal blood clotting. This was followed by injection of lipid nanoparticles that deliver a CRISPR/Cas9 nuclease designed to insert the FVIII coding sequence behind a strong natural liver cell promoter (LNP). The mice given both the AAV and the lipid nanoparticles were able to express normal human FVIII levels, and repeat dosing of the nanoparticles after a single dose of AAV was able to incrementally increase FVIII expression.
“Our experimental therapy has several advantages over existing approaches,” said Dr. Brooks. “The first is that it is theoretically stable for a lifetime because it is integrated into the host’s genome. The second advantage is that you can repeat-dose the LNP component to achieve the desired level of FVIII expression. While gene therapy approaches currently in clinical development that use only the AAV component have resulted in FVIII expression in patients, the level of FVIII is unpredictable in individuals and cannot be changed once it is established.”
The abstract and presentation are available for download at https://casebia.com/news/.
About Casebia Therapeutics
Casebia Therapeutics is a novel joint venture between Bayer and CRISPR Therapeutics, formed in 2016 to advance CRISPR/Cas9 gene-editing therapeutics to discover and develop curative treatments for patients suffering from genetic diseases of the eye, ear and blood, as well as autoimmune, metabolic and cardiovascular conditions. The Casebia technology platform is moving genetic medicine forward by enabling new genetic engineering tools and revolutionary delivery methods for gene editing that target treatments precisely to specific areas of the body affected by disease. Casebia has offices in Cambridge, MA and in San Francisco, CA. For more information, please visit www.casebia.com or follow us at on Twitter @casebiatx.