SUPRO-GEN, Supramolecular polyamine gene vectors for cancer therapy SUPRO-GEN
Supramolecular Polyamine Gene Vectors for Cancer Therapy
H2020 MSCA-RISE 2020 Project SUPRO-GEN, Grant Agreement No 101008072
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Project overview

We are developing supramolecular polyamine gene vectors to increase the efficiency and specificity of cancer treatment by immunotherapy and cancer stem cell therapy.

Gene therapy, most commonly using viral vectors, can be applied to inhibit or edit the expression of any gene of interest, as it is highly specific. Optimal gene therapy vectors should be capable of transporting different types of nucleic acids and in sufficient quantity, should be able to protect their cargo from nucleases, and avoid rapid elimination in the blood. Furthermore, vectors should not cause toxicity or activate an immune response, should have no non-specific interactions with proteins or with cells that are not of interest, and should be able to enter the target cell and escape the endosome.

Although viral vectors for gene therapy are very effective, they are limited in their cargo size, can lead to immunogenic and mutagenic responses and are difficult to produce on a large scale. Therefore, there is an urgent need to find non-viral vectors with low toxicity and high transfection and targeting efficacies.

The aim of the SUPRO-GEN project is to design nanoarchitectonic non-viral vectors based on polyelectrolytes and lipids through supramolecular self-assembly. The vectors will be developed to increase the efficiency of gene therapy using silencing siRNA technologies and BAC transposon/transposase editing in cancer therapies. The vectors will be optimized to enhance nucleic acid loading and facilitate cytoplasmic delivery of siRNAs or nuclear delivery for plasmids. Specificity for tumor targets will be established by peptide and glyco-engineering of the vector surface. A comprehensive study of the cytotoxicity and biological fate of the vectors in vitro, in vivo, and at the cellular level is a fundamental aspect of the research objectives.

SUPRO-GEN is a concerted action based on multidisciplinary expertise in materials science, chemistry, genetic engineering, cancer biology, cancer therapy, and imaging. The project brings together a talented consortium of academic groups from Spain, Italy, Israel, the United States, South Africa, Argentina and Thailand.

In addition to fulfilling our scientific objectives, SUPRO-GEN also aims to develop highly skilled professionals at the interface of materials science and engineering and the biological sciences. The project actively facilitates the transfer of skills and knowledge through work exchanges of early stage and experienced researchers between the participating organizations, and through networking and training activities. Researchers conducting exchanges will develop new scientific and complementary skills while being exposed to new research environments and scientific cultures.

Scheme outlining method of PAH/siRNA assembly

Nature Reviews Genetics 2011, 12: 329-340
Nature Reviews Genetics 2015, 16: 543-552
Drug Discovery Today 2008, 13: 842-855
ACS Nano Letters 2016, 16: 842-848