Research Project
10405974
Project Summary/Abstract Large animal models are critically needed to develop regenerative medicine therapeutics and maximize safe translation to the clinic, as the FDA recommends data be provided on both small and large animal models for approval of such therapies. Using R24 funding (OD019813), we developed biocontainment facilities and protocols to raise an Artemis (DCLRE1C) mutant SCID pig model (ART) as well as an improved model also mutant in IL2RG (ART-IL2RG). The use of SCID pig models in preclinical research necessitates the ability to safely ship healthy SCID pigs across the United States to interested scientists who do not have the ability to raise such pigs themselves. The following two Aims address this existing deficit in the SCID pig research field: Aim 1. Create methods to safely transport SCID pigs within a HEPA filtered isolator transported in a HEPA filtered trailer to researchers in the US and Canada Aim 2. Improve the biosecurity and health of SCID pigs by creating a shower-in facility and purchase dedicated sterilization equipment. As there is no established method to ship SCID pigs while maintaining biocontainment, work in Aim 1 will focus on development of a transportation system consisting of a customized trailer and internal isolators will make this critical next step possible. The transportable internal isolators are needed both to safely house the SCID pigs as well as short- distance transportation from facility biocontainment bubbles to the sterilized trailer for long-distance transport. Further, this revised plan expands the type of clientele who can use the SCID pig, as the isolators containing the SCID pig can be maintained at an external site for short-term research studies. In Aim 2, we continue to develop effective protocols for SCID pig rearing and have identified that isolators are a useful adjunct to the originally proposed and validated bubble procedures. Biosecurity of the SCID pigs will be dramatically improved by the addition of a shower-in facility and purchase of dedicated hydrogen peroxide vaporizer adequately sized for sterilizing these new spaces and equipment. We propose to use A&R funds to renovate unused space adjacent to the existing biocontainment bubbles to provide this shower-in facility and raise the level of biosecurity for SCID pig housing to the industry standard. The sterilization equipment, consisting of a dedicated hydrogen peroxide vaporizer capable of handling the existing bubbles and the proposed new transportation approach in Aim 1, is critically needed as existing equipment is inadequate. The proposed Supplemental Aims do not expand the scope of the existing parent grant and are directly responsive to the call for A&R supplements.
