The discovery of CRISPR genome editing technology has greatly enhanced the potential to treat diseases. However, delivering genome editing components safely and effectively has proven to be challenging. The current lack of specific programmability is a key limiting factor for successfully scaling this technology. A variety of delivery approaches, including but not limited to those below, could potentially meet the need to target tissues and/or cells to advance these technologies into the clinic. To date, lipid nanoparticles (LNPs) are the most well studied non-viral targeted delivery systems. They are specialized for encapsulating nucleic acids and can be altered with ligands to improve delivery specificity. Compared to other synthetic polymer nanoparticles, LNPs have better biocompatibility and lower levels of toxicity. Currently, the liver is the most efficiently targeted organ for LNP based therapeutics. However, due to low delivery efficiency to primary cells and in in vivo animal experiments, the editing efficiency of LNPs is yet to meet clinical requirements in extra-hepatic tissues. After LNPs, polymer-based nanoparticles (PNPs) are the most used delivery vehicles. PNPs offer several benefits over LNPs since they are easier to manufacture, can be varied easily, and have improved circulation time. Inorganic nanoparticles are also gaining popularity as a vehicle for CRISPR based machinery due to their ability to be modified and their efficacy as a carrier for nucleic acids and small molecules. Other bio-inspired delivery vehicles such as exosomes, liposomal drug delivery systems, antibody/protein carriers, virus-like particles such as bacteriophages and nanobots have shown potential but have remained largely underutilized in the genome editor delivery field.
Solutions must be a highly efficient and programmable delivery system to deliver genome editing machinery that can target specific tissues (cells, types, and/or organs). Solutions must be able to be programmed to deliver to at least three distinct and different cell(s), tissue types, and/or organs and with delivery and editing capability that is at least as efficient as the current state of the art. An optimal solution would be straightforward to manufacture, low-cost, scalable and have a reasonable safety profile. Solutions that propose viruses and viral-like systems or particles must build on the field and meet the criteria demonstrating full understanding of how the delivery system can be modified so that it is programmable and can target a variety of different tissue targets (cells, types, and/or organs). The solution will be judged on how well it meets the criteria.
Programmable solutions that only target central nervous system (CNS) targets should be submitted under Target Area 2. Solutions that meet the requirements for Target Area 2 but also are programmable to target a non-brain organ may be submitted for consideration in both Target Areas, though solutions submitted to both Target Areas are only eligible for one prize.
To be highly competitive in this Challenge, Solutions must:
Be programmable and target at least three distinct and different cell(s), tissue types, and/or organs.
Be able to deliver an editor and demonstrate delivery and editing that be at least as efficient as the current published efficiencies for the different tissue targets (cells, types, and/or organs) proposed.
Have a known biological mechanism for programmability: a clear relationship between what is done to modify the technology to deliver to different tissue targets (cells, types, and/or organs) and how this relates to the underlying biology and/or biochemistry of the system.
Have conducted studies that demonstrate biodistribution and route of administration/delivery method.
Demonstrate successful delivery and editing performance in large animals through NIH-supported independent evaluation.
Have demonstrated a safety profile in experimental models consistent with other gene therapy/gene editing delivery systems intended for use in humans.
Solutions should also have these desired traits:
Target more than one tissue/organ type.
Be innovative in approach.
Additionally, solutions could:
Demonstrate market potential, competitive advantage, or potential to meet unmet medical needs.
Be able to be manufactured in a scalable and cost-effective manner.