Project Grant R21EB036298
- This Project Grant from the National Science Foundation's Technology, Innovation, and Partnerships program totaling $100,000 will support research to develop next-generation clustered regularly interspaced short palindromic repeat (CRISPR) systems for curing inherited diseases. Specifically, the awardee, the University of California, Berkeley, will work to circumvent in vivo delivery challenges with CRISPR-Cas9 by developing miniature RNA-guided genome editors smaller than Cas9 that can be...
- Acrigen Biosciences, Inc. was awarded a $1,000,000 cooperative agreement from the National Science Foundation under the Engineering program (CFDA 47.041) to develop a curative gene therapy for spinal muscular atrophy. Over the two year period from March 2022 to February 2024, Acrigen will engineer an anti-CRISPR protein to increase the precision and safety of CRISPR-Cas gene editing. They will pair this with a novel CRISPR nuclease and validate the system for editing and disease correction in...
- The federal Project Grant award, titled "ENHANCEMENT OF GENOME EDITING IN HEMATOPOIETIC STEM CELLS BY NUCLEIC ACIDS NANOPARTICLES DELIVERY OF CRISPR/CAS SYSTEM", was granted by the National Heart Lung and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837). The $486,291 award, effective February 1, 2025 through January 31, 2028, supports the development of a nucleic acid nanoparticle technology to efficiently deliver the CRISPR/Cas9 system into...
- This $322,020 Project Grant award from the National Science Foundation's (NSF) Division of Integrative Organismal Systems will support collaborative research at the University of California, Davis (UC Davis) to develop improved methods for CRISPR/Cas9-based gene editing in maize. The key objectives are to generate maize lines expressing high levels of Cas9 nuclease and to engineer and optimize viral vectors to efficiently deliver guide RNAs for both somatic and heritable gene editing. This...
- Summary Active Motif, Inc. received a $306,094 Project Grant award from the National Human Genome Research Institute (NHGRI) under the Human Genome Research program (CFDA 93.172), with performance extending from September 20, 2025, through August 31, 2026. The award funds the development of a novel epigenetic editing platform that utilizes an innovative targeting approach to recruit epigenetic effectors to specific genomic loci. This platform enables targeted alterations to the epigenome and...
- This $725,512 project grant awarded by the National Science Foundation (NSF) Biological Sciences program (CFDA 47.074) aims to develop highly efficient and robust prime editing systems in rice, tomato, and poplar plants. Prime editing is an advanced CRISPR/Cas gene editing technology that enables precise gene modifications, offering significant advantages over conventional CRISPR approaches. The project will optimize prime editor proteins, improve prime editor guide RNA structures and...
- This $1,211,545 Project Grant award from the National Science Foundation (CFDA 47.074 - Biological Sciences) will support the development of advanced Prime Editing (PE) systems in rice, tomato, and poplar plants. Prime Editing is a novel and highly versatile CRISPR-based gene editing technology that enables precise genome modifications. The key objectives of this 3-year project are to optimize Prime Editor proteins to increase their activity and editing efficiency, improve pegRNA structure and...
- This $1,000,000.00 Project Grant awarded by the National Science Foundation (NSF) Biological Sciences program (CFDA 47.074) supports research to characterize the molecular mechanisms by which the bridge helix (BH) region of the CRISPR-associated (Cas) 9 and Cas12a enzymes contributes to DNA cleavage fidelity. The overarching goal is to develop error-proof variants of these genome editing tools that minimize unintended off-target DNA modifications. The award includes a sub-grant to the University...
- The National Institute of Neurological Disorders and Stroke (NINDS) awarded a $339,999 Project Grant under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) to Couragene, Inc., a for-profit organization located in Edison, New Jersey. The grant supports the development of a novel, chemically modified ribonucleoprotein (CRNP) delivery system for CRISPR-based gene editing to treat Angelman syndrome, a neurogenetic disorder. The project aims to optimize...
- This $199,997 federal Project Grant, awarded by the National Science Foundation's Engineering program (CFDA 47.041), aims to improve the stability and sensitivity of a heat-resistant version of the CRISPR-Cas13 enzyme for rapid and accurate detection of disease-causing RNA. The collaborative research project between William Marsh Rice University and its partners will leverage mechanism-based protein engineering and electrochemical devices to generate next-generation RNA detection tools for...
DEVELOPMENT OF POTENT AND SAFE CRISPR TOOLS FOR IN VIVO GENE EDITING USING DIRECTED EVOLUTION - DEVELOPMENT OF POTENT AND SAFE CRISPR TOOLS FOR IN VIVO GENE EDITING USING DIRECTED EVOLUTION ABSTRACT GENOME EDITING, OR THE ABILITY TO PRECISELY MANIPULATE DNA, IS AN EMERGING TECHNOLOGY THAT HAS THE POTENTIAL TO BE A PERMANENT CURE FOR DEADLY AND DEBILITATING GENETIC DISEASES. THE DEVELOPMENT OF CRISPR- CAS9 AS A GENOME EDITING TOOL HAS CATAPULTED THIS FIELD FROM PRIMARY RESEARCH TO CLINICAL TRIALS WITHIN THE PAST DECADE. CRISPR HAS ALREADY BEEN SUCCESSFULLY USED TO TREAT MULTIPLE DISEASES IN HUMAN CLINICAL TRIALS, INCLUDING HEREDITARY BLINDNESS, NEURODEGENERATION, BLOOD DISORDERS, AND CANCER. AS THESE TREATMENTS GROW IN COMPLEXITY AND ENTER MORE PATIENTS, WE INCREASINGLY NEED ADVANCED CRISPR-CAS9 TOOLS THAT ENABLE POTENT GENE CORRECTION WHILE IMPROVING SAFETY FROM ABERRANT TOXIC AND IMMUNOGENIC EFFECTS. CAS9 IS FAVORED FOR MANY GENOME EDITING APPROACHES DUE TO THE EASE OF REPROGRAMMING; THE CRISPR SINGLE GUIDE RNA (SGRNA) DICTATES TARGET SITE THROUGH BASE PAIRING TO A USER-DEFINED SEQUENCE. HOWEVER, EUKARYOTIC CELLS DISPLAY ROBUST CELLULAR AND IMMUNOGENIC RESPONSES TOWARDS RNAS, LEADING TO SGRNA INSTABILITY AND TOXICITY. CHEMICAL RNA MODIFICATION OVERCOMES THIS ISSUE BY PROTECTING THE OLIGONUCLEOTIDE FROM CELLULAR RNA-RECOGNIZING MACHINERY, LEADING TO IMPROVED STABILITY, DISTRIBUTION, CELLULAR UPTAKE, AND SAFETY. IMPORTANTLY, FULL CHEMICAL MODIFICATION (MODIFICATION AT EVERY RESIDUE) HAS BEEN ESSENTIAL FOR THE THERAPEUTIC SUCCESS OF ESTABLISHED RNA THERAPEUTICS, LIKE SILENCING RNA (SIRNA). DESPITE THE PROMISES OF FULL CHEMICAL MODIFICATION, FULLY MODIFIED SGRNA REMAIN POORLY ACTIVE FOR CAS9 GENOME EDITING, LIKELY DUE TO THE COMPLEX INTERACTIONS BETWEEN THE CAS9 AND SGRNA BEING INCOMPATIBLE WITH CHEMICAL MODIFICATION. THIS PROPOSAL DESCRIBES AN APPROACH TO ENGINEER CAS9 PROTEINS TOWARDS COMPATIBILITY WITH FULLY CHEMICALLY MODIFIED SGRNA. THESE CAS9:SGRNA PAIRS WOULD ENABLE HIGHLY EFFICIENT, EASY TO DELIVER, AND IMMUNE EVASIVE GENOME EDITING, SUPPORTING GENOME EDITING APPLICATIONS INCLUDING MULTIPLEXED TARGETS, TRANSIENT EDITING, REDOSING, AND VECTOR INACTIVATION.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $230.0k | 5/5/26 | ||
| Not listed | $230.0k | 4/30/25 | ||
| Not listed | $276.0k | 5/3/24 | ||
| Not listed | $276.0k | 5/3/24 |