Ioanna Eleftheriadou wins award at ESGCT 20th Anniversary Congress

Ioanna Eleftheriadou won the Special CNS Poster Award at the European Society of Gene and Cell Therapy (ESGCT) 20th Anniversary Congress.

Congratulations to Ioanna Eleftheriadou who won the Special CNS Poster Award at the European Society of Gene and Cell Therapy (ESGCT) 20th Anniversary Congress. 

In collaboration with the French Society of Cell and Gene Therapy, the Congresswas held in Versailles from 25 to 29 October. The ESGCT and Spanish Society for Gene and Cell Therapy (SETGyC) Collaborative Congress 2013 will take place in Madrid from 24 to 27 October 2013.

Abstract

Ioanna Eleftheriadou, Antonio Trabalza, Stuart Ellison and Nicholas Mazarakis, ‘Development of Novel Targeted Lentiviral Vectors for Gene Therapy of Motor Neuron Diseases’

Motor Neuron Diseases (MND) including Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA) are neurodegenerative diseases that can cause progressive paralysis and premature death, while there are no treatments available up to date. Gene therapy using lentiviruses has been successful at alleviating symptoms and extending survival in murine models of both. Lentiviral tropism is determined by their viral envelope proteins, which upon identification and interaction with their receptors induce fusion of the viral envelope with the target cell membrane. Restricting infection to specific cells, known as ‘targeted transduction’, is critical for safe and efficient in vivo gene delivery. An alternative to pseudotyping could be modification of the viral surface through genetic engineering.

The aim of this study was to generate novel lentiviral vectors with tropism to motor neurons (MNs) via the neuromuscular junction (NMJ). Targeting is based on a method that involves incorporation of an antibody and a fusogenic protein into lentiviral surface as two distinct molecules. We have cloned and engineered membrane-bound and single-chain antibodies against rat Thy1.1 and p75LNGFR presynaptic terminal receptors. The resulting high titer vectors were proven to be absolutely specific for Thy1.1 and p75 expressing cells respectively. The targeting specificity of these vectors has extensively been assessed in vitro on target cell lines through a series of binding and competition assay experiments. In vivo intramuscular delivery of these vectors to rat and mouse gastrocnemious muscles is currently being performed to assess retrograde transport to spinal cord and transduction of spinal MNs. These vectors have the potential to be innovative tools for gene transfer to MNs.