Home > Events > Past, present and future of AAVbased gene therapy: capsid evolution and translational vectorology
Centenary Institute - Medical Research
Centenary Institute - Medical Research


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Past, present and future of AAVbased gene therapy: capsid evolution and translational vectorology

18/09/2018 @ 12:00 pm - 1:00 pm

Dr Leszek Lisowski
Group Leader, Translational Vectorology & Manager, Vector and Genome Engineering Facility, CMRI Westmead

Recombinant viral vectors derived from adeno-associated viruses (AAVs) have emerged as the leading technology for gene transfer in the field of translational virology. More recently, an unprecedented efficiency of AAV-driven genome editing without the need for endonucleases has been reported, opening new avenues for the clinical applicability of this “simple” vector system. This new development has positioned rAAV vectors as an attractive, and potentially safer, alternative to well-established CRISPR and ZFN gene editing tools. It also provides new hope for bridging the gap between currently available strong diagnostic powers and therapeutic benefit / improved health outcomes. However, despite exciting in vivo preclinical data from multiple animal models and
evidence of early success in the treatment of Haemophilia B, Parkinson’s disease and Leber’s congenital amaurosis (LCA), clinical data accumulated from over 160 phase I/II/III AAVbased gene therapy trials convincingly demonstrate that current generation rAAV vectors remains unable to efficiently transduce human cells. Thus, for AAV-based gene therapy to achieve its full potential, novel vectors preselected on human target tissues are needed.

In his talk, Dr. Lisowski will introduce and provide an overview of rAAV selection strategies aiming at identification of novel vector variants with desired (pre)clinical properties. The talk will highlight impacts of the selection process and selection system utilized on the function of identified candidates. Dr. Lisowski will provide examples of how rAAV and genome editing tools can be combined to increase the efficiency and translational potential of both technologies. Finally he will discuss the recently discovered novel property of AAV vectors – their ability to drive endonuclease independent genome editing.

Dr Lisowski main research interest is the genetic engineering of viral vectors and genome engineering for use in gene therapy approaches. Trained as a molecular biologist in graduate school, he developed and performed safety evaluation of lentiviral vectors for the treatment of β-thalassemia. Dr Lisowski undertook postdoctoral training in the laboratory of Dr. Mark A. Kay at Stanford University, one of the leaders in the field of adeno-associated virus (AAV) vectorology and liver diseases, where he worked on recombinant AAV vector design, production, and evolution via multispecies interbreeding. He developed novel rAAV vectors capable of specific integration and transgene expression from safe genomic loci and demonstrated successful gene editing in induced pluripotent stem cells (iPS) and embryonic stem cells using zinc finger nucleases. In Dr. Kay’s lab he also improved AAV shuffling technology and identified the first human-specific rAAV vector, which is currently in clinical studies targeting liver. Following his postdoctoral training Dr Lisowski was recruited by the Salk Institute for Biological Studies to run Gene Transfer, Targeting and Therapeutic (GT3) facility that specialized in viral vector development and manufacturing. In 2015 he was recruited by Children’s Medical Research Institute to establish his independent research team, Translational Vectorology Group (TVG) and to establish and manage Vector and Genome Engineering Facility (VGEF). His ongoing research concentrates on the studies of AAV vectorology, development of AAV Directed Evolution technologies, AAV-based genome engineering without the use of endonucleases and liver biology. In addition, he is interested in development of novel biologically predictive animal models of human tissues and human diseases, including HCC, pancreatic cancer and human immune system. Finally, his tea, specializes also in development and improvement of vector manufacturing technologies, with special interest in GMP vector manufacturing.


12:00 pm - 1:00 pm
Event Category:


Centenary Institute Lecture Theatre, Building 93, Royal Prince Alfred Hospital Camperdown, New South Wales 2050 Australia