This February, a new Michelson Grant project will initiate at the University of Newcastle in Callaghan, Australia that will combine the efforts of two previous Michelson Grant recipients, Drs. Lee Smith and John Aitken. The project entitled “Development of nano pharmaceutical strategies for the sterilization of domestic cats and dogs” builds upon technologies developed in their previous projects while introducing new drug delivery technologies that are currently used in humans.
Within the male gonads (i.e. testes) are two cell types (Sertoli and Leydig) that are necessary for the maintenance of sperm development and maturation. Without the support functions of these two cell types, mature sperm cell pools would not develop, thus resulting in an infertile male. This new project aims to permanently disrupt both cell types by delivering a gene to Sertoli and Leydig cells that will cause cell death. The genetic payload will be delivered intravenously by a lipid sphere called a nanoparticle which protects the DNA inside until being internalized into the target cells. In order to target the nanoparticles to the Sertoli and Leydig cells specifically, nanoparticles can be designed to incorporate small peptide sequences on their surface that bind to receptors present on the target cells (i.e. FSH and LH receptors on Sertoli and Leydig cells) thereby adding a level of safety preventing the gene drug from being internalized by non-Sertoli and non-Leydig cells.
The introduction of genes into cells to treat human and animal disease is coming of age and has been primarily built upon the use of either viral vectors or nanoparticle technologies. The use of viral vectors requires the modification of the virus’s genome to incorporate the genes of interest to be introduced. The virus is then manufactured with this DNA inside. Viral vectors are limited in their ability to be modified to introduce targeting peptides on their surface as is needed in this project. In contrast, nanoparticles can be formulated with different ratios of the various lipid components that form the sphere that protects the DNA until it enters the cell. Because of this versatility of manufacturing, many interactions of the nanoparticle components and targeting ligands bound to the surface of the nanoparticle can be tested with ease.
We are looking forward to working with Drs. Smith and Aitken on this project over the coming years. This new use of nanoparticle technology in our research portfolio is exciting and a great complement to our viral vector projects underway. You can learn more about all of the projects that we’ve funded to date by visiting our Research Findings page.
