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MT13-008: Transduction of hematopoietic stem cells to stimulate RNA interference for treatment of feline infectious peritonitis

Feline coronavirus (FCoV) infection is ubiquitous in domestic cats, and while most FCoV-­‐infected cats are healthy, or display only mild enteritis, a small number develop fatal feline infectious peritonitis (FIP) for which there is no treatment. Small-­‐interfering RNAs (siRNAs) are small pieces of RNA that can guide the cell’s own machinery to inhibit viral replication and, thus, possibly provide a potential treatment. These siRNAs work well in cell culture, but an efficient means to deliver this material into a cat’s body is currently lacking.

Therefore, since it is not possible to simply inject the siRNAs into cats due to siRNAs instability in blood, this project proposes modification of blood stem cells, isolated from feline bone marrow, by introducing genetic material that will direct the production of these siRNAs within the stem cells. Following modification, the stem cells could eventually be transfused back into the cat. Division of these altered blood stem cells will result in many daughter cells (macrophages) that will now have the ability to inhibit viral replication.

Macrophages are the site for replication of the coronavirus. It is speculated that virus replication will be reduced enough to allow the cat’s immune system to control the infection. The goal of this project is to test the ability to efficiently, safely, and reproducibly introduce the genetic material into stem cell cultures and to test whether these transduced cells will produce RNAs that inhibit coronavirus replication.

Grant ID: MT13-008

Status: Active

Year Funded: 2013

Amount awarded: $19,453

Investigator: Rebecca P. Wilkes, DVM, PhD, University of Tennessee, College of Veterinary Medicine