Programs and Activities Highlights
- Invertebrate Models Fact Sheet
ORIP revised its fact sheet on invertebrate models. ORIP reviewed the existing section for accuracy and added a link to “MAGIC tools,” a genetic tool for genome-wide mosaic analysis of Drosophila resources. This fact sheet is one of several fact sheets that serve as valuable resources for potential investigators to learn about ORIP resources and programs.
- Nonhuman Primate Resources Fact Sheet
ORIP revised its fact sheet on Nonhuman Primate Resources. ORIP reviewed the fact sheet for accuracy and added information on two resources: the Biospecimens Query System of the National Primate Research Centers Consortium and the Primate Pathology Image Database. This is one of several fact sheets that serve as valuable resources for potential investigators to learn about ORIP resources and programs.
- Swine Models Fact Sheet
ORIP created a new fact sheet on Swine Models. Swine have become valuable models for cardiovascular diseases, diabetes, heart and lung transplantation, and xenotransplantation. This fact sheet lists valuable ORIP-supported resources and initiatives in a concise and comprehensive manner. This is one of several fact sheets that serve as valuable resources for potential investigators to learn about ORIP resources and programs.
- National Primate Research Centers Directors Biannual Meeting
The National Primate Research Centers (NPRCs) Directors Meeting was held in spring 2024. During this meeting, the Directors and other NPRC staff provided information and updates on their centers. The NPRC Program complements and enables the missions of NIH institutes and centers by providing the animals, facilities, expertise, and resources for nonhuman primate research in specific disease areas.
- 2024 U42 Specific-Pathogen-Free Macaque Colonies Steering Committee Meeting
ORIP scheduled and organized the annual meeting of the U42 Specific-Pathogen-Free (SPF) Macaque Steering Committee held May 8, 2024. Attendees included U42 SPF macaque colony principal investigators, other key people associated with the U42 SPF colonies, and OAR and NIH staff. Information presented during the meeting will help ORIP make future recommendations and budget justifications for new initiatives and programs.
Read more in the archive.
ORIP-Supported Research Highlights
- Disruption of Myelin Structure and Oligodendrocyte Maturation in a Macaque Model of Congenital Zika Infection
Using a pigtail macaque model for Zika virus infection, researchers show that in utero exposure of a fetus to Zika virus due to maternal infection results in significantly decreased myelin formation around neurons. Myelin is a protective sheath that forms around neurons and is required for brain processing speed. Damaged myelin resulting from Zika infection in utero is likely a contributing factor to the severe deficits in brain development and microcephaly that result from maternal Zika virus infection.
- AAV5 Delivery of CRISPR/Cas9 Mediates Genome Editing in the Lungs of Young Rhesus Monkeys
Genome editing in somatic cells and tissues has the potential to provide long-term expression of therapeutic proteins to treat a variety of genetic disorders of the lung. However, delivering genome-editing machinery to disease-relevant cell types in the lungs of primates has remained a challenge. Investigators of this article are participating in the NIH Somatic Cell Genome Editing Consortium. Herein, they demonstrate that intratracheal administration of a dual adeno-associated virus type 5 vector encoding CRISPR/Cas9 can mediate genome editing in rhesus (male and female) airways. Up to 8% editing was observed in lung lobes, including a housekeeping gene, GAPDH, and a disease-related gene, angiotensin-converting enzyme 2. Using single-nucleus RNA-sequencing, investigators systematically characterized cell types transduced by the vector.
- Engineered IgM and IgG Cleaving Enzymes for Mitigating Antibody Neutralization and Complement Activation in AAV Gene Transfer
Recombinant adeno-associated viral (AAV) vectors have emerged as the leading platform for therapeutic gene transfer, but systemic dosing of AAV vectors poses potential risk of adverse side effects, including complement activation triggered by anti-capsid immunity. In this report, investigators discover an IgM cleaving enzyme (IceM) that degrades human IgM, a key trigger in the anti-AAV immune cascade. They engineered a fusion enzyme (IceMG) with dual proteolytic activity against human IgM and IgG. Antisera from female mice and rhesus macaques of both sexes treated with IceMG show decreased ability to neutralize AAV and activate complement. These studies have implications for improving the safety of AAV gene therapies, as well as broader potential applications, including organ transplantation and autoimmune diseases.
- Single-Component Multilayered Self-Assembling Protein Nanoparticles Presenting Glycan-Trimmed Uncleaved Prefusion Optimized Envelope Trimers as HIV-1 Vaccine Candidates
Researchers are interested in engineering protein nanoparticles to mimic virus-like particles for an HIV-1 vaccine. In this study, researchers explored a strategy that combines HIV envelope glycoprotein (Env) stabilization, nanoparticle display, and glycan trimming. They designed a panel of constructs for biochemical, biophysical, and structural characterization. Using female mice, female rabbits, and rhesus macaques of both sexes, they demonstrated that glycan trimming increases the frequency of vaccine responders and steers antibody responses away from immunodominant glycan holes and glycan patches. This work offers a potential strategy for overcoming the challenges posed by the Env glycan shield in vaccine development.
- Surgical Protocol for Partial Heart Transplantation in Growing Piglets
Researchers are interested in using partial heart transplantation (i.e., only the part of the heart containing the necessary heart valve is transplanted) to deliver growing heart valve implants. This novel technique allows partial heart transplants to grow, similar to the valves in heart transplants. More work is needed, however, to understand the underlying biological mechanisms of this approach and achieve progress in clinical care. In the current study, the authors present a surgical protocol for partial heart transplantation in growing piglets (sex not specified). This model will enable other researchers to seek fundamental knowledge about the nature of partial heart transplants.
Read more in the archive.
