Non-viral gene delivery vectors: what is known and what is not

Gene delivery is the transfer of genetic material into recipient cells to alter some functions. As the spontaneous entry of intact nucleic acids into cells is unfortunately very inefficient, cationic lipids and polymers, collectively known as non-viral delivery systems, have made their breakthrough in basic and medical research. Such molecules do self-assemble with polyanionic nucleic acids to give rise to nano- and micro-particles that are taken up by cells to elicit their function. Since non-viral vectors currently available do unfortunately suffer from low transfection efficiency and remarkable toxicity, there is an urgent need of more effective vehicles and new tools for the straightforward and quantitative assessment of transfection efficiency and cytotoxicity at once. This talk will chronicle the road towards the development of more and more effective gene delivery vectors. In this regard, major strides forward have been recently made in the development of stimuli-responsive gene delivery vectors that actively respond to changes in the (micro)environment (e.g., cell enzymes, redox status and pH) by altering their properties and behavior. Besides, easy-to-use lab-on-chip platforms to perform transfection assays for unbiased, high-throughput selection of more and more effective gene delivery vectors will be presented as well. Selected references: • Maiolo D*, Colombo J, Beretta J, Malloggi C, Candiani G*, Baldelli Bombelli F. The polyplex, protein corona, cell interplay: Tips and drawbacks. Colloids Surf B Biointerfaces. (2018). DOI: 10.1016/j.colsurfb.2018.01.040 • Giupponi E, Visone R, Occhetta P, Colombo F, Rasponi M, Candiani G*. Development of a microfluidic platform for high-throughput screening of non-viral gene delivery vectors. Biotechnol Bioeng. (2018). DOI: 10.1002/bit.26506 • Pezzoli D, Giupponi E, Mantovani D, Candiani G*. Size matters for in vitro gene delivery: investigating the relationships among complexation protocol, transfection medium, size and sedimentation. Sci Rep. (2017). DOI: 10.1038/srep44134 • Malloggi C, Pezzoli D, Magagnin L, De Nardo L, Mantovani D, Tallarita E, Candiani G*. Comparative evaluation and optimization of off-the-shelf cationic polymers for gene delivery purposes. Polymer Chem. (2015). DOI: 10.1039/C5PY00915D • Pezzoli D, Zanda M, Chiesa R, Candiani G*. The yin of exofacial protein sulfhydryls and the yang of intracellular glutathione in in vitro transfection with SS14 bioreducible lipoplexes. J Control Release. (2013). DOI: 10.1016/j.jconrel.2012.10.016