Novel vectors for gene therapies targeting primary human Schwann cells

The recent gene therapy clinical successes hinge on continuing progress in the development of AAV­ based gene delivery systems, driven primarily by advances in AAV capsid technology. In this project we will capitalize on the proprietary AAV variants recently developed in our laboratory, which can efficiently transduce primary human Schwann cells (hSCs), but not human fibroblasts. As liver is the natural target for all natural AAVs and thus a major off-target organ in human clinical applications, we will take advantage of our patented Functional Transduction (FT) AAV bioengineering platform and our unique access to the most clinically predictive preclinical model of human liver, a xenograft mouse repopulated with primary human hepatocytes, to de-target the novel variants from the liver. Finally, we will use non-human primates (NHPs) to assess toxicity of our newly developed AAV capsids with unprecedented delivery to primary hSCs. Ultimately, our goal is to develop the most functional AAV vector with decreased human liver tropism and capable of avoiding AAV NAbs, for efficient hSCs targeting following systemic administration.

Investigators

Leszek Lisowski, PhD

The University of Sydney

Ian Alexander, PhD

The Sydney Children's Hospitals Network

Kristi Jones, PhD

The Sydney Children's Hospitals Network

Gloria Gonzalez-Aseguinolaza, PhD

Universidad de Navarra

Leszek Lisowski, PhD

The University of Sydney

Ian Alexander, PhD

The Sydney Children's Hospitals Network

Kristi Jones, PhD

The Sydney Children's Hospitals Network

Gloria Gonzalez-Aseguinolaza, PhD

Universidad de Navarra

Current Stage

Discovery

Discovery
In Vivo Proof of Concept
IND Enabling
Clinical Trial Phase 1
Clinical Trial Phase 2
Clinical Trial Phase 3