Extending our CRISPR/Cas9 platform with in vivo approaches
We are building on the expertise we have gained through our ex vivo programs to pursue in vivo therapies, in which we plan to deliver CRISPR/Cas9 either systemically or into specific target organs in the body. We believe this approach has the potential to cure a variety of devastating genetically-defined diseases.
Viral and non-viral approaches to in vivo delivery
Currently, several methods exist to deliver DNA or RNA to cells inside the body, which we can adapt to deliver CRISPR/Cas9 components. These methods fall into two broad categories: viral and non-viral. We are developing therapeutic programs based on technologies in both these areas.
Non-viral: Our efforts into non-viral delivery methods have focused on lipid nanoparticles (LNPs), which predominantly target the liver. We can encapsulate messenger RNA (mRNA) encoding Cas9 and guide RNA, and a donor DNA template if necessary, into LNPs to shuttle these components to the liver. We have entered into partnerships with the Massachusetts Institute of Technology (MIT) for LNP technology and CureVac for mRNA to support our liver-targeted programs
Viral: For other organ systems, including the muscle, lung and central nervous system, we have emphasized viral delivery, primarily using adeno-associated viral (AAV) vectors. These vectors can deliver DNA encoding for Cas9 and guide RNAs into specific tissues of the body. Through our collaboration with StrideBio, we aim to engineer novel AAV vectors that more specifically target individual tissue types and that can avoid pre-existing immunity
In vivo therapies can address a range of genetically-defined diseases
We have established in vivo programs that aim to treat glycogen storage disease type Ia (GSD Ia) and, with our partners at Vertex Pharmaceuticals, Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1) and cystic fibrosis (CF). We also have two collaborations directed towards applying CRISPR/Cas9 gene editing in the central nervous system: one with Target ALS and the University of Florida that focuses on amyotrophic lateral sclerosis (ALS), and another with the Friedreich's Ataxia Research Alliance (FARA) and the University of Alabama at Birmingham that focuses on Friedreich's ataxia (FA).
To learn more about our specific in vivo programs, please visit our pipeline