Programs and Activities Highlights
- Notice of Funding Opportunity: Resource-Related Research Projects for Development of Models and Related Materials for Studying Human Health and Diseases (R24 Clinical Trials Not Allowed)
ORIP encourages grant applications aimed at developing, characterizing, or improving research models for human health and diseases; developing biology-based new approach methodologies (NAMs) applicable to human health and diseases; or improving access to information about or generated from the use of models for human disease. The models, including NAMs, and related biological materials developed must be broadly applicable to the scientific interests of two or more NIH institutes or centers and must evaluate diseases and processes that impact multiple organ systems in alignment with ORIP’s NIH-wide mission and programs.
- Precision Model Centers Introductory Meeting
ORIP organized and presented at the Precision Model Centers Introductory Meeting on September 15, 2025. This virtual meeting included principal investigators and project leads of ORIP’s renewed U54 Division of Comparative Medicine (DCM) initiative, the Precision Model Centers Consortium. Program officials of the projects (DCM) and project scientists (Division of Construction and Instruments) attended the meeting, presented the plan for the new cycle, discussed collaborations, and planned future meetings.
- International Mouse Phenotyping Consortium Network Call
An ORIP staff member presented an NIH update on new approach methodologies (NAMs) and the use of animals in research at the International Mouse Phenotyping Consortium (IMPC) network call on August 12, 2025. The IMPC monthly call includes members of the IMPC, as well as NIH staff. ORIP’s presentation was devoted to the current NIH policies regarding use of animals in research, as well as NAM initiatives. Attendees discussed implementation of the policies and their potential effect on Knockout Mouse Project/IMPC activities.
- Cryopreservation Workshop, Session V: Long-Term Preservation Methods for Nonhuman Primate Models in Biomedical Research
ORIP hosted the Cryopreservation and Other Preservation Approaches for Animal Models Workshop to address topics related to cryopreservation and other preservation methods. Session V, held on July 15, 2025, focused on long-term preservation of nonhuman primate models for biomedical research. This session brought together experts in the field to discuss current state-of-the-art techniques, as well as challenges and barriers in the field. A summary of the workshop will be posted on the ORIP website.
- Wonderous Worms: Unearthing New Insights Into Health
NIH News in Health published an article titled “Wonderous Worms: Unearthing New Insights Into Health” in July 2025. This article included quotes from Dr. Ann Rougvie, an expert in Caenorhabditis elegans biology and principal investigator of the ORIP-supported Caenorhabditis Genetics Center. The article was reviewed by three ORIP grantees: Drs. David Hall, Nathan Schroeder, and David Sherwood.
Read more in the archive.
ORIP-Supported Research Highlights
- A Porcine Model of Fanconi Anemia
Fanconi anemia (FA) causes birth and developmental defects because of disrupted DNA repair. Without the ability to repair DNA damage, mutations continue to collect in the patient’s tissues, which leads to anemia, bone marrow failure, and cancer. Mouse and rat models for FA do not mimic the key clinical symptoms of FA, such as anemia. A pig model of FA could accurately mimic many of the clinical features seen in human patients because pigs have similar physiology and a relatively long lifespan. Researchers targeted the FANCA gene in domestic pigs. The FANCA porcine model (sex not stated) showed skeletal abnormalities, extreme sensitivity to agents that cause DNA crosslinks (a type of DNA damage), hematopoietic progenitor cell reduction, enlarged red blood cells, and reduced neutrophil (a type of immune cell) numbers in peripheral blood. Mitomycin C treatment resulted in a tenfold increase in chromosomal radials—where a segment of one chromosome breaks off and attaches to another, causing unbalanced rearrangements due to improper DNA repair—which is a diagnostic marker for FA in patients. This study shows that the FANCA porcine model is a promising preclinical model for developing strategies to prevent bone marrow failure and malignancies in FA patients.
- Long-Acting Lenacapavir Acts as an Effective Preexposure Prophylaxis in a SHIV Challenge Macaque Model
Preexposure prophylaxis (PrEP) is a form of medicine that protects a person from getting a disease rather than having to treat them after they get sick. Daily oral PrEP is an effective way to prevent new HIV infections, but it must be taken as instructed. PrEP that requires less-frequent doses would make it easier and more convenient to keep taking the medication and would reduce clinical visits. Using 3- to 5-year-old male rhesus macaques, researchers showed that a single dose of lenacapavir injected beneath the skin produced sustained levels of the drug in plasma. It also provided strong preventive activity against a high-dose simian-human immunodeficiency virus (SHIV) administered rectally. No drug resistance emerged, and SHIV infections occurred only when the drug level fell below the target needed for complete protection. These findings give researchers critical data about dosing intervals, protective concentrations, and the long-acting potential of lenacapavir. This knowledge will support lenacapavir’s progression to human HIV PrEP trials.
- Long-Acting Lenacapavir Protects Macaques Against Intravenous Challenge with Simian-Tropic HIV
Lenacapavir is a U.S. Food and Drug Administration–approved drug for treating multidrug-resistant HIV and needs to be taken only twice a year. Preexposure prophylaxis (PrEP) is a form of medicine that protects a person from getting sick rather than having to treat them after they get a disease. Because lenacapavir shows long-acting drug activity, it may be an ideal candidate for PrEP, as current PrEP medications require daily dosing. Researchers used experiments in vitro (in the lab, outside of a living organism) to show that lenacapavir has strong antiviral activity. Using 4- to 9-year-old male pigtail macaques (PTMs), researchers showed that a single dose of lenacapavir injected beneath the skin protected the PTMs from simian-tropic HIV-1 virus. After 419 days, researchers depleted T cell (a type of immune cell) levels in the PTMs and showed that low-level viral infections did not emerge. This study supports the evidence for moving lenacapavir into human PrEP development.
- A Thymus-Independent Artificial Organoid System Supports Complete Thymopoiesis from Rhesus Macaque–Derived Hematopoietic Stem and Progenitor Cells
The creation of T cells (specialized blood cells protecting the body from infections and diseases) involves many steps that begin with T cell progenitor cells (cells that become T cells) in the bone marrow. T cells finish developing and multiply in the thymus. Although nonhuman primates (NHPs) serve as key models for studying T cell development and output under normal and disease conditions, no non-animal technology for T cell development and output currently exists. To address this gap, researchers developed a rhesus macaque (RM)–specific organoid (3D cell cultures that contain several cell types and mimic specific functions of an organ). This NHP organoid mimics thymopoiesis (a series of events leading to the creation of T cells) in a thymus-tissue-free environment. This study is the first to demonstrate an NHP-specific artificial thymic organoid that models thymopoiesis and can be used in future research studies to understand T cell development and output in different diseases.
- In Utero Rescue of Neurological Dysfunction in a Mouse Model of Wiedemann-Steiner Syndrome
Wiedemann-Steiner syndrome (WDSTS) is a rare, autosomal-dominant (only one mutated gene copy is needed for symptoms to develop) genetic disorder that causes intellectual disability, abnormal facial features, and reduced growth. WDSTS occurs when the histone lysine methyltransferase 2A (KMT2A) protein is mutated. In previous studies using mouse models, syndromes related to WDSTS, such as Rett and Kabuki, have shown promise in being treatable after birth. The researchers created a mouse model for WDSTS (both sexes included) and showed that the genetic disorder could be treated in the womb by restoring KMT2A protein function. This model could be used in future studies to identify possible therapies and the window for treatment.
Read more in the archive.
