Programs and Activities Highlights
- 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.
- Notice of Extension of the Expiration Date for RFA-OD-22-013, Resource-Related Research Projects for Development of Animal Models and Related Materials (R24, Clinical Trials Not Allowed)
ORIP published a notice to extend the expiration date for RFA-OD-22-013, Resource-Related Research Projects for Development of Animal Models and Related Materials (R24, Clinical Trials Not Allowed). RFA-OD-22-013 now expires on September 26, 2025. ORIP’s intent with this funding opportunity is to support resource-related research projects that are aimed at developing and characterizing new resources; improving existing resources; or acquiring deep understanding of a model system to improve the utilization, accessibility, and translational values of models to the research community.
- International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project Annual Fall Meeting
The International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project (KOMP) Annual Fall Meeting was held on September 15–16, 2024. An ORIP staff member monitored overall project progress and exchange of scientific knowledge of the international collaboration, contributed to the discussions, conducted an in-depth review of the data provided, and crafted meeting conclusions. The meeting conclusions were communicated to the NIH KOMP Working Group and ORIP and DPCPSI leadership.
- Czech Centre for Phenogenomics Conference 2024
An ORIP staff member represented the International Mouse Phenotyping Consortium–Knockout Mouse Phenotyping Project at an international community phenotyping conference on September 17–18, 2024. He participated in discussions regarding the use of animal models for the development of preclinical drug testing pipelines, as well as genome editing therapeutics.
Read more in the archive.
ORIP-Supported Research Highlights
- In Vivo Prime Editing Rescues Alternating Hemiplegia of Childhood in Mice
Alternating hemiplegia of childhood (AHC) is a neurodevelopmental disease that can cause involuntary muscle contractions, low muscle tone, paralysis on one side of the body, abnormal eye movements, seizures, and intellectual disability. There currently is no treatment. AHC is caused by a mutation in the gene ATP1A3; three variations of the ATP1A3 gene mutation are responsible for 65% of cases. Researchers used prime editing and base editing tools to correct ATP1A3 gene mutations in cells isolated from AHC patients and two mouse models for AHC (sex not specified). Results showed that physical characteristics of AHC were corrected and that treated mice had an extended lifespan. These findings support the potential use of prime editing and base editing tools to treat this neurological disease.
- Determinants of Successful AAV-Vectored Delivery of HIV-1 bNAbs in Early Life
More than 100,000 children are infected with HIV each year through vertical (mother-to-child) transmission. Antiretroviral treatment lapses can occur during postpartum care, which then increases levels of HIV in the mother, resulting in an increased risk of transmission to the infant through breastfeeding. Broadly neutralizing antibodies (bNAbs) defend the host from pathogens and have shown potential as a safe therapy for infants. Gene transfer using adeno-associated virus (AAV) offers an opportunity to provide preventive care for infants at risk of getting HIV. Researchers used an infant rhesus macaque model (sex not specified) for simian immunodeficiency virus (SIV)—equivalent to HIV but in nonhuman primates—to determine whether a single intramuscular injection of AAV-bNAb could protect against SIV vertical transmission. The therapy was more effective in newborn rhesus macaques than in older infants and juveniles, and the newborns also were less likely to develop anti-drug antibodies. Results showed that functional antibodies were present even after 4 years. These findings support the possible use of AAV-bNAb to protect infants from contracting HIV.
- Multiplexed Proteomic Biosensor Platform for Label-Free Real-Time Simultaneous Kinetic Screening of Thousands of Protein Interactions
Existing methods for producing functional protein libraries are costly and time-consuming, and they lack real-time kinetic (protein interaction) screening abilities. Researchers developed an automated platform for high-throughput production and screening of a library of proteins on biosensor surfaces. Biosensors are devices that can bind a specific protein in a sample containing many proteins to generate a measurable signal unique to the protein of interest. This allows researchers to complete large-scale kinetic measurements for drug discovery, biomarker identification, and diagnostic development. The platform created by the researchers is known as the Sensor-Integrated Proteome On Chip (SPOC®). SPOC uses nanowells to capture 2,400 proteins at the same time on a single gold biosensor chip. The SPOC biosensor chip can then be analyzed with different techniques to generate kinetic data. The SPOC will allow researchers to understand protein interactions on a large scale for research and clinical applications.
- miR-33 Inhibition as a Novel Therapeutic Approach for Treating Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a devastating disorder caused by changes in the dystrophin gene sequence, which results in the absence of a functional dystrophin protein. Several microRNAs (a type of RNA that can bind to other molecules) can alter DMD by changing gene expression. In this review article, the authors discuss inhibiting microRNAs as a new therapy for DMD. Researchers have shown in a DMD mouse model (sex not specified) that blocking miR-33a/b, a microRNA, can improve muscle regeneration (regrowth of damaged tissue) and reduce DMD symptoms. Anti-microRNA oligonucleotides (AMOs) are short chains of DNA or RNA that block microRNAs. Injection of an AMO that blocks miR-33a/b in the DMD mouse model improved muscle regrowth and increased gene pathways involved in muscle regrowth. These studies highlight the impact of microRNA signaling pathways in DMD and show how they could serve as targets for new therapies to treat the disease.
- Distinguishing PEX2 and PEX16 Gene Variant Severity for Mild, Severe, and Atypical Peroxisome Biogenesis Disorders
Peroxisomes are structures in cells that play an important role in metabolism and chemical changes of complex fats. Peroxisomal biogenesis disorders (PBDs) are caused by mutations in peroxin (PEX) genes. PBDs are autosomal recessive diseases—a mutated PEX gene must be passed down from both parents. In patients, symptoms of PBD range from mild to severe multi-organ system defects depending on gene mutations and even different mutations in the same gene. Researchers wanted to understand how different mutations cause the variation in symptoms seen in patients. In fruit flies, the researchers replaced the fly Pex genes with two human PEX genes—PEX2 and PEX16—and different mutant forms of these genes. Researchers found that some mutations caused severe symptoms, such as seizure-like behavior, while others were milder. Introducing a normal functional copy of the human PEX genes into the flies with mutant Pex genes alleviated the symptoms. Further studies with fruit flies will help us understand how different PEX gene mutations affect PBD severity in patients.
- Functional Analysis of Pathogenic Variants in LAMB1-Related Leukoencephalopathy Reveals Genotype–Phenotype Correlations and Suggests Its Role in Glial Cells
Cells are surrounded by a matrix, known as the basement membrane, that provides structural support and enhances signaling. Laminin B1 (LAMB1) is a matrix protein in the basement membrane that helps form this supportive structure around cells. Mutations (mistakes in the DNA sequence) in the LAMB1 gene can cause rare neurological disorders. Researchers studied the fruit fly version of the LAMB1 gene, which is LanB1. Using fruit flies, the researchers were able to gain insight into the link between LAMB1 gene mutations and disease symptoms. The LanB1 protein is found in a subset of brain cells, called glia cells, and in the blood–brain barrier. Reducing the amount of LanB1 protein in the blood–brain barrier caused shorter lifespans and movement defects in the fruit flies. Human LAMB1 was not functional in flies, but fly experiments showed that some LanB1 mutations cause severe defects, while others were milder. Tests in human cells suggested some LAMB1 mutations might cause disorders, even in the presence of a normal copy of LAMB1. This study reveals the role of LanB1 in keeping the healthy structure of the fly blood–brain barrier and understanding the consequences of different LAMB1 mutations in humans.
Read more in the archive.
