Agenda

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) have recently moved into the realm of stand‐alone therapeutic agents for the treatment of diseases with established genetic targets. These include genetic diseases, cancer, infectious diseases, cardiovascular diseases, musculoskeletal and nervous system diseases. This success has stemmed from the appreciation that both nucleic acids carry out myriad functions that go beyond mere storage of genetic information and protein synthesis. In contrast to conventional small molecules and biologic drugs, which generally induce transient therapeutic effects because they target proteins rather than underlying causes, nucleic acid-based therapeutics can achieve long-lasting and possibly curative therapeutic effects in inherited and acquired disorders. However, irrespective of the large diversity of biochemical and therapeutic mechanisms, through which the diverse DNA- and RNA-based therapeutics can act, their clinical translation has been often limited by their unfavourable physicochemical characteristics that ultimately prevent their facile transmission to the desired tissues and into the cells. To overcome these barriers and enable safe and effective delivery of nucleic acids to the correct target tissue and cell type, scientists around the world, over the years, have developed different delivery platform technologies. However, while these technologies led to nucleic acid-based therapeutics with superior stability and ultimately improved pharmacokinetics and pharmacodynamics profiles, the “precise” delivery of a given nucleic acid to a specific tissue or cell remain an unsolved issue. To tackle this challenge, a team of scientist of Ca’ Foscari University and the European Centre for Living Technologies (ECLT) have proposed to use a novel type of nanocarrier capable of binding with high affinity and selectivity cell surface tissue-specific receptors that have historically been resistant to conventional modalities.
Their project A novel integrated cyclic peptide-based platform for precision delivery of nucleic acid-based therapeutics (ALLIANCE), has been recently evaluated positively the National Center for Gene Therapy and Drugs based on RNA Technology (CN RNA & Gene Therapy) securing a funding of more than 700K euro. The project foresee the involvement of a research team formed by scientists with consolidated expertise in biochemistry, biophysics, chemistry and computational sciences, a mix that guarantees a multidisciplinary approach and an integrated scientific environment, all necessary for the success of such ambitious research program. The nanocarriers proposed by our scientists have qualities typical of chemical and biological molecules. They possess: high binding affinity and exquisite specificity, small size, ease of chemical synthesis, high thermal and proteolytic resistance, low immunogenicity and excellent biocompatibility and biodegradability.
All these properties make them similar to “miniaturized antibodies” and represent an unprecedent and attractive modality for the development of next generation nucleic acid-delivery systems with better tissue-selectivity, lower toxicity, and superior efficacy for a wide range of diseases. Generation of cyclic peptides potentially capable to precisely ferry nucleic acid-based therapeutics to a given tissue will be achieved by applying a combination of experimental and computational key enabling technologies. If successful, such technology will not only have an impact on the health of patients but could also have remarkable scientific, technological and economic implications.

Research Team
Alessandro Angelini
Achille Giacometti
Alessandro Scarso
Fabrizio Fabris
Flavio Romano
Federico Polo
Giulia Fiorani
Marco Nobile
Marta Simeoni
Tatjana Skrbic