Polyplus gene delivery tool poised for Phase II

The trial involves the delivery of nucleic acids for cancer therapy by means of a plasmid combined with the in vivo -jetPEI transfection reagent, Polyplus-transfection said.

No further details were available from the Strasbourg-based company.

Polyplus-transfection is positioning the reagent as a cheaper synthetic alternative to traditional viral methods of gene delivery, with additional advantages such as, importantly, avoidance of the inflammatory immune response that complicates gene therapy involving viral vectors and prevents their repeated use in patients.

The Phase II trial can go ahead because Polyplus-transfection has now produced the first batch of the in vivo -jetPEI reagent generated in full compliance with good manufacturing practice (GMP).

Last year the company started preliminary work on bringing in vivo -jetPEI production up to GMP standard after receiving an €80,000 grant from France's Muscular Dystrophy Association (AMF).

With in vivo -jetPEI, customers have the option of "using the same transfection reagent from the early stages of preclinical research to clinical trials in humans" , Polyplus-transfection notes adding that the reagent "is able to transfect effectively both in vitro and in vivo - which is not the case with most of the commercially available transfection reagents" .

A Drug Master File (DMF) giving detailed information on the manufacturing process for in vivo -jetPEI has been filed with the US Food and Drug Administration, hence simplifying the documentation needed for clinical trial applications, Polyplus-transfection noted.

"The GMP-compliant availability of our leading product for human clinical use is a crucial advantage in the choice of a transfection agent for therapeutic projects," said Joëlle Bloch, chief executive of Polyplus-transfection.

"It will speed up the growth of all Polyplus' in vivo transfection agents."

Phase I/II cancer gene therapy and AIDS trials using GMP-grade reagents from Polyplus-transfection are already underway in Israel, the US and Hungary.

Last September, the company signed a collaboration agreement with US RNAi therapeutics specialist Alnylam Pharmaceuticals, under which Alnylam is evaluating Polyplus' formulations for the delivery of RNAi therapeutics.

In June 2007, the French company set up the Polyplus in vivo consortium, an international network of research scientists and clinicians using the company's gene therapy reagents.

The aim is that the consortium members, who will receive personalised support from Polyplus-transfection, will share experiences and know-how, thereby accelerating clinical development of the reagents.

In vivo -jetPEI is derived from the synthetic molecule polyethylenimine (PEI), a cationic linear polymer for which Polyplus-transfection holds an exclusive worldwide licence for the transfection of nucleic acids.

The delivery reagent works by condensing nucleic acids into small nanoparticles of 50nm that remain stable for several hours.

These nanoparticles are small enough to diffuse into tissues and enter cells by endocytosis, whereby in vivo -jetPEI facilitates the release of the enclosed DNA into the cell, achieving the desired therapeutic effect through expression of the gene.