Programs and Activities Highlights
- ORIP Concept Clearance (Reissue): Development of Models, New Approach Methodologies, and Biological Materials for Studying Human Health and Diseases (R21 Clinical Trial Not Allowed)
An ORIP staff member presented a concept to the NIH Council of Councils on September 10, 2026, to continue ORIP’s R21 program. The R21 program supports the development and improvement of research models, biological resources, technologies, and new approach methodologies (NAMs). The program has produced widely used research tools and resources and has helped support larger research projects. The reissued program will align with the ORIP 2026–2030 Strategic Plan and will focus on projects that can benefit multiple NIH institutes, centers, and research areas.
- 2026 Meeting of the Centers for Precision Disease Modeling Consortium
ORIP organized and conducted the annual meeting of the Centers for Precision Disease Modeling Consortium on June 4, 2026. The consortium was established to provide the biomedical community with advanced models needed to develop precision therapies for monogenic and complex disorders. Meeting participants included ORIP staff, principal investigators, and team representatives.
- ORIP Workshop: Advancing Research Infrastructure to Study Human Diseases
The Advancing Research Infrastructure to Study Human Diseases workshop was held on June 8 and 12, 2026. The workshop offered a platform to discuss complementary approaches to addressing complex biological mechanistic questions related to expanding NIH-funded model resources and physical infrastructure, validating new approach methodologies (NAMs), and improving the predictability and scalability of models for human diseases. Day 1 of the workshop addressed the strategic and translational integration of NAMs and animal models in biomedical research. Day 2 of the workshop focused on presenting emerging NAMs technologies that will advance human disease research, with an emphasis on strategies for integrating and validating combinatorial NAMs. A meeting report and video recording will be posted on the ORIP website at a later date.
- INCLUDE Project: Transformative Research Awards for Down Syndrome (R01 Clinical Trial Not Allowed)
The NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project seeks to improve the health and quality of life for individuals with Down syndrome. ORIP has signed onto this notice of funding opportunity, which invites researchers to submit applications for supporting groundbreaking, exceptionally innovative, original, and/or unconventional research that has the potential to create new scientific paradigms, establish entirely new and improved clinical approaches, or develop transformative technologies related to Down syndrome.
- Access to Genetically Engineered Mouse Resources
During the 22nd Workshop on the Pathology of Mouse Models for Human Disease, an ORIP staff member presented on access to genetically engineered mouse resources. The workshop was held both virtually and in person from April 20–24, 2026, at St. Jude Children’s Research Hospital in Memphis, Tennessee.
Read more in the archive.
ORIP-Supported Research Highlights
- Environmental and Developmental Factors Shape Anti-AAV Immunity in Pigs
Adeno-associated viruses (AAVs) show promise for delivering gene therapies to treat monogenic (caused by changes in a single gene) diseases. Researchers evaluated the utility of pigs (sex not stated) as models for testing AAV-based therapies. Consistent with previous studies, they showed that pigs naturally produce antibodies (protective proteins made by the immune system) that can block AAV vectors. These antibodies appeared by 2 weeks of age and increased over time. Immune responses also varied by environment, with pigs in standard housing showing stronger and more diverse responses than those in highly controlled settings. Removing IgG (a type of antibody found in blood and extracellular fluid) restored AAV activity in laboratory tests. This study suggests that pigs can help researchers test ways to overcome immune barriers associated with gene therapies.
- Genome-Wide Association Mapping and Targeted Loss of Function Studies Identify Shroom3 as a Driver of Hyperpolyploidy and Ventricular Dilation
Cardiomyocyte polyploidy (a condition where heart muscle cells replicate their DNA but fail to divide) is associated with responses to cardiac injury, but researchers do not fully understand the mechanisms explaining this effect. Researchers studied heart muscle cells in rats (both sexes used) and found that cells with extra chromosome copies were linked to weaker heart pumping and enlarged heart chambers. By scanning rat genomes, they identified the gene Shroom3 as an important driver of this process. When Shroom3 was disrupted in heart cells, polyploidy increased and heart function worsened. The findings suggest Shroom3 helps control heart cell structure and may offer clues for understanding heart disease.
- Vaccination Elicits HIV Broadly Neutralizing Antibodies in Primates
The HIV envelope glycoprotein (a molecule in the outer layer of the virus) plays an important role in starting viral infection. However, this protein has high antigenic variability, which makes it difficult to create an effective vaccine against HIV. In this study, researchers designed and optimized a series of HIV vaccine antigens that used a germline-targeting approach—a novel vaccine strategy that aims to guide the development of broadly neutralizing antibodies (bnAbs)—to prime rare precursor immune cells to develop into cells that produce bnAbs capable of recognizing diverse HIV strains. The most promising vaccine candidates were tested in 24 rhesus macaques (RMs) (both sexes used). Results showed vaccine administration created bnAb-class memory B cells (immune cells). Forty-four percent of RMs showed serum bnAb activity, and bnAb serum levels showed promise in protecting against a broad range of HIV isolates. These findings provide proof of concept for the germline-targeting strategy and support the goal of creating a broadly protective HIV vaccine, which has long been out of reach.
- A Universal 6iL/E4 Culture System for Deriving and Maintaining Embryonic Stem Cells Across Mammalian Species
Embryonic stem cells (ESCs) can become many different types of cells during embryonic development. Obtaining ESCs from embryos remains a challenge for biomedical research. In this study, researchers developed a serum-free culture system—6iL/E4—that allows ESCs to be acquired from different animal models. This culture system also allows ESCs to self-renew (divide into new cells forever). Results showed successful use of this system for mouse, rat, rabbit, and cow embryos. The culture system required an extra drug to successfully obtain rabbit ESCs. Several cell-signaling pathways—GSK3α, WNT, STAT3, PDGFR, and MEK/ERK—were shared across the different species and allowed ESCs to remain in an early, flexible cell state. The culture system also was able to maintain human pluripotent stem cells (cells that develop into many different types of cells). This system may serve as a universal platform to support stem cell research, disease modeling studies, and biotechnology development.
- Patient-Specific Midbrain Organoids with CRISPR Correction Recapitulate Neuronopathic Gaucher Disease Phenotypes and Enable Evaluation of Novel Therapies
Gaucher disease (GD) is caused by a mutation in the GBA1 gene that causes accumulation of specific molecules, leading to inflammation and neurodegeneration (a decline in the nervous system and brain). Neuronopathic GD (nGD) is a severe form of GD, and preclinical models do not fully mimic the disease. In this study, researchers developed brain-like organoids (3D cell cultures) from nGD patient cells (sex not stated). Results showed that these organoids display key disease features, including reduced enzyme activity levels, buildup of harmful lipids (fat), and disrupted brain cell development. Using a gene-editing technique, researchers corrected the GBA1 mutation in the organoids and observed a reduction in these disease characteristics. The researchers also tested three possible treatments: enzyme delivery using nanoparticles, gene therapy, and a drug that reduces fat production. These treatments showed promising results for restoring normal function. These findings highlight the utility of patient-derived nGD organoids for identifying the underlying mechanisms of GD, testing new therapies, and supporting personalized treatment development.
Read more in the archive.
