The arrival of lipid nanoparticles has revolutionised the field of gene therapy. Also used in the development of mRNA-based vaccines against COVID-19, lipid nanoparticles have shown great success in clinical applications. However, the ability of these particles to effectively encapsulate large DNA molecules still remains an understudied field.

The research of Sapienza University's NanoDelivery Lab, coordinated by Giulio Caracciolo and Daniela Pozzi, aims to fill this gap. In the study published in Nature Communications, carried out in collaboration with other Italian and European institutes such as the Istituto Pasteur Italia, the Scuola Normale Superiore of Pisa and the Technical University of Graz in Austria, and with the support of the CERIC-ERIC (Central European Research Infrastructure Consortium), the researchers obtained particles with a unique morphology that demonstrate an improved transport capacity compared to traditional formulations, opening the way to new targeted gene therapies.

The designed technology uses lipid nanoparticles capable of incorporating large DNA. The resulting particles are then further engineered and coated with a biomolecular crown made of DNA and plasma proteins: following this modification, the resulting lipid nanoparticles become a true biological nano-architecture capable of evading the immune system and increasing the effectiveness of gene therapy.

“The innovative approach of our study demonstrates an improved DNA transport capacity compared to classical formulations, while ensuring greater stability and reduced immune response - says Giulio Caracciolo of Sapienza University - This could enable the correction of genetic defects and provide tools for the fight against cancer, representing an important step towards innovative therapies for diseases that are difficult to treat with the methods currently used in clinical practice”.

References:

Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery - Renzi, S., Digiacomo, L., Pozzi, D. et al. - Nature Communications (2024) https://doi.org/10.1038/s41467-024-53569-8

Further Information

Giulio Caracciolo
Department of Molecular Medicine
giulio.caracciolo@uniroma1.it

Saula Checquolo
Department of Medical - Surgical Sciences and Biotechnology
saula.checquolo@uniroma1.it

Alessandra Zingoni
Department of Molecular Medicine
alessandra.zingoni@uniroma1.it