Recent advancements in the genome editing technology field have enabled scientists to manipulate genomic sequences rapidly and efficiently. Despite revolutionary progress in this area, several challenges remain. Existing gene editing technologies like CRISPR-cas9, base editors and prime editors have great potential, but existing delivery technologies are not able to deliver gene editing technologies to many target tissues and cell types in sufficient quantities, which hinders clinical applications. While some cell types, like hepatocytes in the liver, have many delivery technologies capable of delivering genome editors, there are many other organs and cell types that are harder to reach.
The Targeted Genome Editor Delivery (TARGETED) Challenge is a $6,000,000 challenge to improve the current state of in vivo delivery technologies for genome editors in two Target Areas: 1. Programmable Delivery System for Gene Editing, and 2. Crossing the Blood-Brain Barrier. The National Institutes of Health (NIH), through the Common Fund’s Somatic Cell Genome Editing (SCGE) program, is seeking Participants with ideas or early-stage solutions to join the Challenge with the chance to win up to $1,000,000 and have their solution independently tested and validated in large animal models through NIH-supported independent evaluation relevant to preclinical assessments of investigational products.
The Challenge is a three-phase competition. In Phase 1, Participants will be asked to submit a proposal describing their proposed solution and how it will address the requirements for one of the Target Areas. Participants may submit proposed solutions to both Target Areas but must do so with separate proposals that independently address each Target Area’s requirements. Up to ten proposals that are judged to best meet the requirements will each be awarded up to $75,000. Additional prizes of $50,000 may be awarded to additional meritorious solutions on the basis of the Judging Criteria. In Phase 2, Participants must submit data from studies that demonstrate delivery and editing performance as well as describe their methodology, technology, and how their solution addresses the Challenge criteria. Participation in Phase 1 is not a requirement for participation in Phase 2; however, it is strongly encouraged. Up to 10 winners of Phase 2 will be each awarded $250,000 and will be eligible to compete in Phase 3. Only Phase 2 winners will be eligible to participate in Phase 3. Phase 3 is separated into Phase 3a and 3b; all Participants must submit solutions for Phase 3a to be eligible to participate in Phase 3b. For Phase 3a, Participants must submit all required information showing that their technology is ready for large animal testing through NIH-supported independent evaluation and has the ability to solve the requirements for one of the Target Areas. Up to 6 Participants will each be awarded $50,000 and will then prepare for reagent scale up and protocol development for NIH-supported large animal testing. Participants who submit their reagents and protocols by the deadline for Phase 3b will have access to NIH-funded independent large animal testing to validate their solution. NIH will review the results and only award prizes to Participants whose solutions meet or exceed the criteria. The top successful solution in each Target Area will be awarded $625,000; the second place solution in each Target Area will be awarded $225,000; the third place solution in each Target Area will be publicly recognized and given an honorable mention award. Participants who participate successfully in all three phases could be awarded up to $1,000,000 in each Target Area.
Final (Phase 3) Solution Requirements
Target Area 1: Programmable Delivery System for Gene Editing
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 a single team and/or entity with a single solution that meets the requirements of both Target Areas are only eligible for one prize. A team and/or entity may be eligible for multiple prizes for multiple solutions submitted to either or both Target Areas, as long as the solutions are qualitatively different.
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.
Target Area 2: Crossing the Blood-Brain Barrier (BBB)
Solutions to Target Area 2 must be highly efficient, non-viral delivery systems capable of crossing the BBB to deliver genome editing machinery to a substantial proportion of clinically relevant cell types in the brain.
To be highly competitive in this Challenge, solutions must:
Be able to traverse the BBB in vivo.
Be able to deliver an editor and demonstrate delivery and editing in a substantial proportion of clinically relevant cell types in the brain.
Be a non-viral delivery technology. Solutions may be virus-like particles and/or incorporate components of viruses in the proposed delivery technology. Solutions that are modifications of recombinant adeno-associated viral vectors do not meet this criterion.
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:
Be innovative in approach.
Be able to be manufactured, ideally synthetically, in a scalable and cost-effective manner.
IP Considerations:
Through the TARGETED Challenge, NIH aims to maximize public access to the winning delivery technology solutions (as defined as the delivery vehicle for the genome editing machinery), and to maximize the number of people who can benefit from therapeutic genome editing utilizing the winning delivery technologies, regardless of the prevalence of their disease. To balance these objectives with encouraging appropriate licensing and commercialization of the technology, the NIH is requiring the inclusion of a Public Access and Dissemination Plan (PADP) as part of the submission. Instructions for how to prepare this are given in the “How to Enter” section.
Partners:
The SCGE program is led by the NIH Common Fund, the National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Disorders and Stroke (NINDS). The Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative and the National Heart, Lung, and Blood Institute (NHLBI) are also contributors to this Challenge.
Challenge Administration: This Challenge is administered and managed with support from Freelancer.com under a contract awarded by the National Aeronautics and Space Administration (NASA) Center of Excellence for Collaborative Innovation on behalf of NIH.
Statutory Authority to Conduct the Challenge
The NIH Common Fund is a component of the NIH budget which is managed by the Office of Strategic Coordination, Division of Program Coordination, Planning, and Strategic Coordination, Office of the Director. Common Fund programs address emerging scientific opportunities and pressing challenges in biomedical research that no single NIH Institute or Center (IC) can address on its own but are of high priority for the NIH as a whole [42 U.S.C. 282a(c)(1)]. The SCGE program is supported by the NIH Common Fund to improve the efficacy and specificity of gene editing approaches, and to accelerate the clinical development of genome editing.
The NIH Office of the Director is conducting this Challenge under the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Reauthorization Act of 2010, as amended [15 U.S.C. § 3719]. This Challenge is consistent with and promotes the agency’s mission by catalyzing the goal-driven development of innovative tools and technologies with the potential to enhance human health.
Supplementary Information:
The TARGETED Challenge is a continuation of NIH’s Common Fund’s Somatic Cell Genome Editing (SCGE) program. The SCGE program aims to improve the efficacy and specificity of gene editing approaches to help reduce the burden of common and rare diseases caused by genetic changes. Thousands of debilitating diseases can be attributed to genetic mutations, such as Huntington’s Disease, cystic fibrosis, and Duchenne Muscular Dystrophy.
In order to treat a disease, a significant number of genome editors must be delivered to the disease-relevant cell type. Getting gene editing tools into sufficient numbers of cells, in the diverse organs associated with different diseases, requires improved delivery technologies. Even in cases where targeted delivery to the desired tissue or cell type is achieved, the efficiency rate—the percentage of cells that are ultimately edited —is typically less than ideal.
Gene editing as a means of treating diseases is an exciting but challenging prospect. In order to realize the full potential of genome editing, there must be transformative advances in the two strategic Target Areas.
Current State of Research
Target Area 1:
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.
Target Area 2
The blood–brain barrier (BBB) is comprised of endothelial cells in the brain vasculature, as well as specialized glial cells (astrocytes) which surround blood vessels in the brain. The BBB prevents unwanted substances from entering into the extracellular fluid of the central nervous system. Given the vital importance of brain function, it is imperative that the influx and efflux of biological substances be carefully controlled for the appropriate functioning of the central nervous system. One practical consequence of the BBB is that it also blocks the uptake of many pharmaceuticals, including proteins and nucleic acids. This hinders development of treatments for brain related diseases. As such, an effective technology to deliver genome editing machinery across the blood-brain barrier to a substantial proportion of clinically relevant brain cell types would have broad implications for the treatment of many neurogenetic diseases.
Awards:- 6,000,000
Deadline:- 11-01-2025
