2021 Ignition Awards Recipients:
The WaNPRC Pilot Program is conducted jointly with the Institute for Translational Health Sciences and provides funding to collect preliminary data for future funding opportunities. The goal is to fund projects with innovative research endeavors that have translational implications to move toward human applications. This year there was a competitive pool of applications and we were able to provide funding to 2 projects.
Please join us in congratulating the Grant Year 60 recipients of the WaNPRC Pilot Program which exemplify the commitment to cutting edge science, collaboration and also support the 3Rs (Reduction, Refinement and Replacement) of animal use.
- Jesse Erasmus, PhD, (University of Washington, Fuller Lab) “Overcoming bottlenecks in mRNA-mediated antibody expression in nonhuman primates”
Abstract: We have demonstrated protection from acute virus infection in mice receiving an intramuscular injection of RNA encoding a monoclonal antibody. While this approach holds promise for enabling rapid development of antibody therapeutics that can be administered in an outpatient setting, scaling intramuscular doses from mice to larger animals has proven difficult, failing in a nonhuman primate pilot study. We have since identified three major bottlenecks in antibody expression in vivo, 1) host translation shutdown mediated by endoplasmic reticulum (ER) stress and plasmacytoid dendritic (pDC) cell interferon production, 2) anti-drug antibody response, and 3) limiting numbers of transfected target cells. We have developed an RNA molecule that co-expresses a modified antibody along with a cell-autonomous human ICAM-1 blocking peptide, designed to reduce ER stress and inhibit local pDC interaction with RNA-transfected cells, respectively. Given the 87% similarity between human and pigtail macaque (PTM) ICAM-1, we hypothesize that in PTMs, this will 1) reduce ER stress- and pDC-mediated interferon production and downstream host translation shutoff, and 2) reduce pDC-mediated anti-drug antibody responses. In order to increase the number of target cells, we propose to use an FDA-approved multi-needle array in order to spread an injection volume over multiple sites.
- Amy Orsborn, PhD, (UW Department of Electrical & Computer Engineering and UW Department of Bioengineering, WaNPRC Core Staff): “Developing and validating a new behavioral assay to quantify feedforward and feedback”
Abstract: Our movements are controlled by a combination of predictive feedforward control and reactive feedback control. Incorporating insights from feedforward/feedback control has significantly improved therapies to restore motor function like brain-machine interfaces. However, existing methods to study motor behaviors in non-human primates (NHPs) cannot quantify and disentangle feedforward and feedback control components. This methodological gap limits our ability to study the neural mechanisms of sensorimotor control. Robust control theory methods have been used to directly quantify feedforward and feedback sensorimotor pathways in humans, but these approaches have not yet been tested in NHPs. We propose a study to develop and validate these behavioral assays in NHPs. We will develop assays for both in-cage assays that may accelerate training (aim 1) and laboratory assays for more complex, higher dimensional movements (aim 2). With expertise in both NHP behavioral training and control theory, our team is positioned to rapidly generate critical feasibility data for future grants. If successful, our proposal will provide primate neuroscientists with new tools to study the neural mechanisms of sensorimotor learning and control. Quantifying feedforward and feedback control and their neural signatures will also enable improved brain-machine interface therapies.
We wish the recipients luck in their endeavors and we look forward to hearing about their exciting results next year.
Elizabeth A. Buffalo, PhD | Interim Associate Director for Research
The WaNPRC performs critical biomedical research leading to new advances in science and medicine. WaNPRC researchers are working to develop effective vaccines and therapies for HIV/AIDS and other infectious diseases as well as new advances in genetics, neuroscience, vision, and stem cell biology and therapy. The WaNPRC directly supports the National Institutes of Health’s mission to translate scientific advances into meaningful improvement in healthcare and medicine.