{"id":270354263,"generated_unique_award_id":"ASST_NON_R41AI192172_075","fain":"R41AI192172","uri":"R41AI192172-3602039179","category":"grant","type":"04","type_description":"PROJECT GRANT (B)","description":"DEVELOPMENT OF A GENE EDITED PLATFORM TO ENABLE HUMAN ALLOGENEIC CELL REPLACEMENT THERAPY - SUMMARY  STEM CELL-BASED THERAPIES HAVE THE POTENTIAL TO REGENERATE CELLS, TISSUES, AND ORGANS DAMAGED BY INJURY, AGE, AND AUTOIMMUNITY. PLURIPOTENT STEM CELL (PSC)-BASED CLINICAL TRIALS HAVE BEGUN IN WHICH RETINAL PIGMENTAL EPITHELIAL CELLS, DOPAMINERGIC NEURONS, AND INSULIN-PRODUCING BETA CELLS ARE USED TO TREAT MACULAR DEGENERATION, PARKINSON’S DISEASE, AND TYPE 1 DIABETES (T1D), RESPECTIVELY. THE INITIAL RESULTS HAVE BEEN QUITE PROMISING, AND CLEARLY THE FUTURE OF THIS AVENUE OF INVESTIGATION AND TREATMENT IS BRIGHT. THE CASE FOR USING THIS APPROACH TO TREAT T1D IS PERHAPS THE STRONGEST, GIVEN THAT MATURE BETA CELL TRANSPLANTS FROM CADAVERS HAVE LONG BEEN SHOWN TO BE CURATIVE, AND INITIAL PSC-DERIVED BETA CELL TRANSPLANTS HAVE ALSO LED TO INDEPENDENCE FROM EXOGENOUS INSULIN. ALEUTIAN THERAPEUTICS IS FOCUSED ON THIS LINE OF TREATMENT FOR CURING T1D. NONETHELESS, THERE ARE MAJOR BARRIERS TO BE OVERCOME TO MAKE THESE TYPES OF PSC-BASED THERAPIES PRACTICAL AND ACCESSIBLE. AUTOLOGOUS IPSC-BASED APPROACHES, FOR INSTANCE, ARE COSTLY AND UNSCALABLE. ALLOGENEIC PSC-BASED APPROACHES, ON THE OTHER HAND, REQUIRE ADMINISTRATION OF TOXIC IMMUNOSUPPRESSIVE DRUGS TO AVOID DESTRUCTION OF TRANSPLANTED CELLS BY THE HOST IMMUNE SYSTEM.  TO OVERCOME THESE LIMITATIONS, ALEUTIAN THERAPEUTICS (ALEUTIAN) IS DEVELOPING A NOVEL GENE EDITING-BASED PLATFORM TO ENABLE ALLOGENEIC PSCS AND THEIR PROGENY TO EVADE RECOGNITION BY THE HOST IMMUNE SYSTEM. ALEUTIAN’S INNOVATIVE APPROACH HAS SUCCESSFULLY DEMONSTRATED SURVIVAL OF PSC GRAFTS IN MICE WITH A FULLY FUNCTIONAL IMMUNE SYSTEM. IN CONTRAST, OTHERS DEVELOPING SIMILAR TECHNOLOGIES HAVE RELIED ON IN VITRO STUDIES OR HUMANIZED MICE, WHICH MAY NOT REPRESENT THE COMPLEXITY OF A NATIVE IMMUNE SYSTEM. IN FACT, ALEUTIAN’S TECHNOLOGY HAS BEEN SHOWN TO ENABLE HUMAN PSC TO SURVIVE FOR NEARLY 6 MONTHS IN IMMUNOCOMPETENT MICE, EFFECTIVELY OVERCOMING THE XENOGENEIC BARRIER, OFTEN REGARDED AS EVEN HIGHER THAN THE ALLOGENEIC BARRIER. HAVING USED THIS APPROACH TO SUCCESSFULLY IDENTIFY THE KEY IMMUNE RECOGNITION PATHWAYS THAT MUST BE EVADED, THE GOALS OF THIS PHASE 1 STUDY ARE TO NOW 1) ADAPT OUR SYSTEM IN WHICH MOUSE IMMUNE EVASION GENES ARE SWAPPED WITH THE FUNCTIONALLY EQUIVALENT HUMAN ORTHOLOGS; 2) DEFINE THE MINIMUM REQUIRED COMBINATIONS OF THESE HUMAN IMMUNE EVASION FACTORS THROUGH FUNCTIONAL ASSAYS; 3) CONFIRM THAT THESE EDITS DO NOT IMPACT BETA CELL DIFFERENTIATION AND ALLOW BETA CELLS TO EVADE THE KEY ARMS OF THE HOST IMMUNE SYSTEM. SUCCESSFUL COMPLETION OF THIS STUDY WILL INFORM THE DESIGN AND GENERATION OF A CRISPR-CAS9 EDITED CELL LINE THAT CAN BE FURTHER EVALUATED IN IN VIVO PRE-CLINICAL STUDIES DURING A PHASE II PROGRAM.","subaward_count":0,"total_subaward_amount":null,"total_subsidy_cost":0.0,"total_loan_value":0.0,"total_obligation":305855.0,"date_signed":"2025-08-18","base_and_all_options":null,"base_exercised_options":null,"non_federal_funding":0.0,"total_funding":305855.0,"total_account_outlay":256854.3,"total_account_obligation":305855.0,"account_outlays_by_defc":[{"code":"Q","amount":256854.3}],"account_obligations_by_defc":[{"code":"Q","amount":305855.0}],"record_type":2,"cfda_info":[{"applicant_eligibility":"Universities, colleges, hospitals, laboratories, and other public or private nonprofit domestic institutions, including State and local units of government, and individuals are eligible to make application for grant support of research by a named principal investigator or a research career development candidate.   For-profit organizations are also eligible, with the exception of NRSA.  Individual NRSA awardees must be nominated and sponsored by a public or nonprofit private institution having staff and facilities appropriate to the proposed research training program. All NRSA awardees must be citizens or have been admitted to the United States for permanent residence.  To be eligible, predoctoral candidates must have completed the baccalaureate degree, and postdoctoral awardees must have a professional or scientific degree (M.D., Ph.D., D.D.S., D.O., D.V.M., Sc.D., D.Eng., or equivalent domestic or foreign degree). SBIR grants can be awarded only to domestic small businesses (entities that are independently owned  and operated for profit, are not dominant in the field in which research is being proposed and have no more than 500 employees).  Primary employment (more than one-half time) of the principal investigator must be with the small business at the time of award and during the conduct of the proposed project. In both Phase I and Phase II, the research must be performed in the U.S. or its possessions.  STTR grants can be awarded only to domestic small business concerns (entities that are independently owned and operated for profit, are not dominant in the field in which researches proposed and have no more than 500 employees) which \"partner\" with a research institution in cooperative research and development.   At least 40 percent of the project is to be performed by the small business concern and at least 30 percent by the research institution.  In both Phase I and Phase II, the research must be performed in the U.S. and its possessions.  To be eligible for funding, a grant application must be approved for scientific merit and program relevance by a scientific review group and a national advisory council.","beneficiary_eligibility":"Any nonprofit or for-profit organization, company, or institution engaged in biomedical research.","cfda_federal_agency":"NATIONAL INSTITUTES OF HEALTH, HEALTH AND HUMAN SERVICES, DEPARTMENT OF","cfda_number":"93.855","cfda_objectives":"To assist public and private nonprofit institutions and individuals to establish, expand and improve biomedical research and research training in infectious diseases and related areas; to conduct developmental research, to produce and test research materials.  To assist public, private and commercial institutions to conduct developmental research, to produce and test research materials, to provide research services as required by the agency for programs in infectious diseases, and controlling disease caused by infectious or parasitic agents, allergic and immunologic diseases and related areas.   Projects range from studies of microbial physiology and antigenic structure to collaborative trials of experimental drugs and vaccines, mechanisms of resistance to antibiotics as well as research dealing with epidemiological observations in hospitalized patients or community populations and progress in allergic and immunologic diseases.  Because of this dual focus, the program encompasses both basic research and clinical research.  Small Business Innovation Research (SBIR) program expands and improves private sector participation in biomedical research.  The SBIR Program intends to increase and facilitate private sector commercialization of innovations derived from Federal research and development; to increase small business participation in Federal research and development; and to foster and encourage participation of socially and economically disadvantaged small business concerns and women-owned small business concerns in technological innovation.  The Small Business Technology Transfer (STTR) program stimulates and fosters scientific and technological innovation through cooperative research and development carried out between small business concerns and research institutions; to foster technology transfer between small business concerns and research institutions; to increase private sector commercialization of innovations derived from Federal research and development; and to foster and encourage participation of socially and economically disadvantaged small business concerns and women-owned small business concerns in technological innovation.   Research Career Development Awards support the development of scientists during the formative stages of their careers.   Individual National Research Service Awards (NRSAs) are made directly to approve applicants for research training in specified biomedical shortage areas.  In addition, Institutional National Research Service Awards are made to enable institutions to select and make awards to individuals to receive training under the aegis of their institutional program.","cfda_obligations":"(Grant) FY 24$2,627,428,812.00; FY 25$3,184,821,868.00; FY 26 est $3,127,494,674.00; - B- Project Grants will have a lower amount then previous fiscal years because the new 2023 CFDA reporting requirements include both B- Project Grants and B- Cooperative Agreements.(Cooperative Agreement) FY 24$1,446,383,717.00; FY 25$1,193,413,771.00; FY 26 est $1,171,932,322.00; - B- Cooperative Agreements are part of the new CFDA reporting guidelines starting in 2023.","cfda_popular_name":"National Institutes of Allergy and Infectious Diseases","cfda_title":"Allergy and Infectious Diseases Research","cfda_website":"http://www.niaid.nih.gov","federal_action_obligation_amount":305855.0,"non_federal_funding_amount":0.0,"sam_website":"https://sam.gov/fal/dab90bbd42704331b5990aaac2ac282f/view","total_funding_amount":305855.0}],"transaction_obligated_amount":305855.0,"funding_agency":{"id":830,"has_agency_page":true,"toptier_agency":{"name":"Department of Health and Human Services","code":"075","abbreviation":"HHS","slug":"department-of-health-and-human-services"},"subtier_agency":{"name":"National Institutes of Health","code":"7529","abbreviation":"NIH"},"office_agency_name":"NIH National Institute of Allergy and Infectious Diseases"},"awarding_agency":{"id":830,"has_agency_page":true,"toptier_agency":{"name":"Department of Health and Human Services","code":"075","abbreviation":"HHS","slug":"department-of-health-and-human-services"},"subtier_agency":{"name":"National Institutes of Health","code":"7529","abbreviation":"NIH"},"office_agency_name":"NIH National Institute of Allergy and Infectious Diseases"},"period_of_performance":{"start_date":"2025-08-18","end_date":"2026-12-31","last_modified_date":"2026-08-05"},"recipient":{"recipient_hash":"1ea4dd83-c77b-a514-8ad3-ce40fe97fb01-R","recipient_name":"ALEUTIAN THERAPEUTICS, INC.","recipient_uei":"E797SLBJB9F1","recipient_unique_id":null,"parent_recipient_hash":null,"parent_recipient_name":null,"parent_recipient_uei":null,"parent_recipient_unique_id":null,"business_categories":["Category Business","Small Business"],"location":{"location_country_code":"USA","country_name":"UNITED STATES","state_code":"CA","state_name":"CALIFORNIA","city_name":"LOS ANGELES","county_code":"037","county_name":"LOS ANGELES","address_line1":"1730 SAWTELLE BLVD PH 9","address_line2":null,"address_line3":null,"congressional_code":"36","zip4":"6177","zip5":"90025","foreign_postal_code":null,"foreign_province":null}},"executive_details":{"officers":[{"name":null,"amount":null},{"name":null,"amount":null},{"name":null,"amount":null},{"name":null,"amount":null},{"name":null,"amount":null}]},"place_of_performance":{"location_country_code":"USA","country_name":"UNITED STATES","county_code":null,"county_name":null,"city_name":null,"state_code":"CA","state_name":"CALIFORNIA","congressional_code":null,"zip4":null,"zip5":null,"address_line1":null,"address_line2":null,"address_line3":null,"foreign_province":null,"foreign_postal_code":null},"total_outlay":256854.3,"funding_opportunity":{"number":"PA-24-247","goals":"NOT APPLICABLE"}}