MIT Technology Review has called CRISPR-mediated gene editing “the biggest biotech discovery of the century.”
Each cell in our body contains a genome of 3 billion base pairs of DNA where even single changes – or mutations – can cause a wide variety of inherited or acquired diseases. CRISPR allows researchers to target disease-associated mutations with unprecedented precision, treating diseases at the underlying cause. Through a process akin to genome surgery, DNA mutations are quite literally edited out of the cell.
CRISPR genome editing requires two components to be delivered into cells: a targeting RNA (guide RNA) and a protein (e.g. Cas9).
Delivery is the Main Barrier to Developing Therapeutics
Many scientists believe the key to unlocking CRISPR’s therapeutic potential is delivery via an adeno-associated virus (AAV), an FDA-approved delivery vehicle with a history of safety, efficacy, and lack of toxicity. Until now, the small size of AAV has been a significant obstacle for the packaging of CRISPR, leaving less safe and less effective therapeutic options. To learn more about the CRISPR delivery problem, see this article from Chemical & Engineering News.
AAV is the Industry Preferred Delivery Vehicle
For decades, AAV has been the industry standard delivery vehicle for in vivo gene therapy, due to its track record of safety, limited toxicity, and immunogenicity. An increasing number of FDA approved trials are using AAV (greater than 200 trials worldwide) and it can deliver materials with high efficiency and specificity to a wide variety of cell types.
Hunterian Solution for CRISPR and AAV
For most CRISPR systems, the problem is that the CRISPR components and requisite elements needed for gene-editing are too big to fit into AAV.
AAV has a cargo capacity of approximately 5.2kb. This has been viewed as insufficient to deliver the SpCas9 CRISPR system, as the protein (Cas9), RNA (gRNA), “instructions” (promoters and terminators), and viral components (ITRs) together exceed 5.2kb by a significant margin.
The Hunterian Solution
A true platform technology.
Hunterian’s technology uses a novel “2-for-1” genetic control element, a bidirectional promoter, to overcome the challenge of delivering CRISPR via AAV. The bidirectional promoter shrinks the “instructions” necessary for in vivo expression of CRISPR, thereby enabling CRISPR delivery well within the limited AAV packaging capacity.
By freeing up critical space in AAV, Hunterian's technology allows for the development of the safest and most effective CRISPR-based therapeutics. Hunterian's approach has the immediate potential to bring multiple CRISPR technologies to the clinic and dramatically accelerate the development of CRISPR-based therapeutics.
Scientists continue to identify a number of CRISPR systems that Hunterian can deliver through a single AAV. Our platform technology enables scientists to target far more regions in the human genome – over a BILLION more than existing technologies – meaning that many more mutations in skeletal or cardiac muscle, lungs, brain, and other tissues can now be addressed using CRISPR technology.
A benefit to solving the delivery problem for SpCas9 is the ability to deliver other novel CRISPR variants, including two next-generation SpCas9 variants that have undetectable levels of off-targets. Additionally, Hunterian technology has been shown by Johns Hopkins scientists to reduce off-target effects when compared to approaches utilized by the other CRISPR technologies.
Hunterian’s platform technology enables greater versatility to address a much broader scope of diseases.
Hunterian Focus Areas
Hunterian is exploring a range of diseases and orphan indications for licensing and/or development, including for diseases that cannot be addressed by current CRISPR technologies.
We are interested in diseases where biopharmaceutical treatments have historically failed and diseases that can be treated—or cured—by editing DNA mutations.