Project Grant R41OD031942
- 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...
- This $546,600 Project Grant awarded by the National Science Foundation's (NSF) Integrative Activities program (CFDA 47.083) aims to engineer mesenchymal stem cell-derived exosomes (MSC-EXO) for targeted immunomodulation and enhanced bone repair. The University of Maryland Eastern Shore (UMES), a historically black, 1890 land-grant institution, is the primary awardee. The key objectives of this 3-year project are to: 1) generate engineered exosomes (TEX) for reprogramming macrophages, 2) modify...
- 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...
- Federal Grant Award Summary The National Heart, Lung, and Blood Institute (NHLBI) awarded the University of Texas at Austin a $564,121 Project Grant (CFDA 93.837: Cardiovascular Diseases Research) effective August 15, 2025, through May 31, 2029, to develop peptide surface-functionalized lipid nanoparticles (PepLNPs) for pulmonary delivery of gene-editing therapies targeting cystic fibrosis (CF). The project focuses on creating nucleic acid delivery systems capable of penetrating the mucus...
- 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...
- Federal Project Grant Award Summary The National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded the University of California, Berkeley $120,393 on May 1, 2026, through the Discovery and Applied Research for Technological Innovations to Improve Human Health program (CFDA 93.286) to develop novel genome editing delivery technologies. The project, which concludes April 30, 2028, focuses on creating lentivirus-derived lipid vesicles (enveloped delivery vehicles) engineered to...
- Summary of Cooperative Agreement Award The University of Florida's Division of Sponsored Research received a $452,378 Cooperative Agreement from the National Institutes of Health (NIH) Office of the Director under the Trans-NIH Research Support program (CFDA 93.310), effective July 1, 2025 through May 1, 2028. This award funds the evaluation and optimization of a high-throughput extracellular vesicle (EV) loading platform designed to advance therapeutic genome editing therapeutics. The project...
- Federal Grant Award Summary The National Heart, Lung, and Blood Institute (NHLBI) awarded Icahn School of Medicine at Mount Sinai a $1.46 million Project Grant under the Cardiovascular Diseases Research program (CFDA 93.837) to develop a versatile paired prime editing toolkit for cystic fibrosis transmembrane conductance regulator (CFTR) gene correction. The award, obligated on August 15, 2025, with a completion date of May 31, 2030, funds the development of genome editing strategies to...
- This Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training Program (CFDA 93.859) provides $364,167 to Villanova University to develop novel non-viral gene delivery methods for cell therapies. The key objectives are: The Bracaglia Lab will develop new polymeric gene delivery vehicles to improve the delivery of siRNAs and other payloads to T cells and hematopoietic stem cells (HSCs). Drs. Elmer and Huang will...
ENGINEERED EXOSOMES FOR TARGETED DELIVERY OF THE CRISPR/CAS9 GENOME-EDITOR - TECHNICAL ABSTRACT GENETIC MUTATIONS HAVE BEEN IDENTIFIED AS A CAUSATIVE FACTOR IN NUMEROUS DISEASES. THE GENOME EDITING SYSTEM CRISPR/CAS9 IS A RECENT DEVELOPMENT IN GENE THERAPY. BOTH VIRAL AND NON-VIRAL VECTORS HAVE BEEN USED IN ATTEMPTS TO DIRECT DELIVERY OF CAS9 TO SPECIFIC LOCATIONS WITH ADVANTAGES AND LIMITATIONS SIMILAR TO THOSE KNOWN FOR OTHER NUCLEIC ACID-BASED THERAPEUTICS. THESE CHALLENGES HAVE LIMITED THE CURRENT CLINICAL PROGRESS OF THIS GENOME-EDITING TOOL. THE GOAL OF THIS PROJECT IS TO DEVELOP AN EFFECTIVE TARGETED DELIVERY SYSTEM FOR CAS9-MEDIATED GENOME EDITING. THE INVESTIGATORS TAKE ADVANTAGE OF A NOVEL TECHNOLOGY FOR DELIVERY OF PLASMID DNA (PDNA) BASED ON BOVINE MILK/COLOSTRUM EXOSOMES DEVELOPED IN THE PI'S LABORATORY. IN THIS PROJECT, WE WILL APPLY OUR KNOWLEDGE AND EXTENSIVE EXPERIENCE IN EXOSOMES FOR EFFICIENT TARGETED DELIVERY OF THE CAS9-MEDIATED GENOME- EDITING TOOL. TO ESTABLISH FEASIBILITY, WE HAVE USED PDNA TO DELIVER THE CODING SEQUENCES FOR CAS9-MEDIATED KNOCKOUT OF NFB AS A MODEL GENE. THIS SINGLE PLASMID, PKO-NFB, CONTAINS THE MAMMALIAN-OPTIMIZED CAS9 CODING SEQUENCE, THE SINGLE-GUIDE RNA (SGRNA) SPECIFIC TO NFB, AS WELL AS SEQUENCES TO DERIVE A GUIDE RNA (GRNA) SCAFFOLD TO ASSIST IN THE BINDING OF CAS9 TO THE TARGET DNA. WE HYPOTHESIZE THAT PKO-NFB, IONICALLY ENTRAPPED IN A NOVEL EXOSOME MATRIX, FORMULATED BY COMPLEXING EXOSOMES AND POLYCATIONIC POLYETHYLENEIMINE (PEI), WILL SERVE AS AN EFFECTIVE GENOME-EDITING TOOL OF NFB. FURTHERMORE, USE OF ENGINEERED EXOSOMES, PREPARED BY LOADING MILK LACTOFERRIN (LF) ONTO EXOSOMES, WILL TARGET BRONCHIAL EPITHELIUM OVEREXPRESSING LF RECEPTORS. THUS, LF-EPM-PKO-NFB ADMINISTERED INTRANASALLY (I.N.) WILL TARGET LUNG WITH MINIMAL OFF-TARGET EFFECTS FOR DELIVERY OF THIS GENOME-EDITING TOOL. OUR HYPOTHESIS IS SUPPORTED BY COMPELLING PRELIMINARY DATA: HIGH LOADING OF NUCLEIC ACID ONTO EPM AND PROTECTION FROM DEGRADATION, FUNCTIONALIZATION OF EXOSOMES BY SURFACE-BOUND LF LOADING, INHIBITION OF NFB EXPRESSION IN H2030 LUNG CANCER CELLS BY LF-EPM DELIVERED PKO-NFB, OVEREXPRESSION OF THE LF RECEPTOR INTELECTIN (ALSO CALLED OMENTIN) IN THE MOUSE LUNG, AND PREDOMINANT DELIVERY OF LF-FUNCTIONALIZED EXOSOMES TO THE MOUSE LUNG BY INTRANASAL DELIVERY. INVESTIGATORS EXPERIENCED IN EXOSOMES, DRUG DELIVERY, AND BIOLOGICAL SCIENCES WILL PURSUE THE FOLLOWING SPECIFIC AIMS: AIM 1. OPTIMIZE TARGETED DELIVERY OF CRISPR/CAS9 GENOME-EDITING TOOL USING ENGINEERED EXOSOMES IN VITRO. AIM 2. DETERMINE POTENTIAL TOXICITY, AND BIODISTRIBUTION AND EFFICACY OF ENGINEERED EXOSOMES FOR TARGETED DELIVERY OF CRISPR/CAS9 GENOME-EDITING TOOL. IF WE ARE SUCCESSFUL IN ACHIEVING THESE MILESTONES, WE WILL MOVE TO PHASE II. RESULTS FROM THIS PROJECT WILL PROVIDE FEASIBILITY DATA FOR ADVANCING THIS GENOME-EDITING TOOL DELIVERY `PLATFORM' IN A DISEASE MODEL. COST-EFFECTIVE ISOLATION OF EXOSOMES FROM A BIOCOMPATIBLE SOURCE, COMBINED WITH ULTRACENTRIFUGATION- INDEPENDENT METHODS CURRENTLY BEING DEVELOPED IN PI'S LABORATORY, MAKES THE EXOSOMES PRODUCTION A COMMERCIAL VIABILITY AS THIS NOVEL DELIVERY TECHNOLOGY ADVANCES.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $0 | 8/20/24 | ||
| Not listed | $264.5k | 5/24/22 |