Functionalised nano-carriers for target-specific delivery of RNA drugs

PI:

Roberto Improta

Email:

roberto.improta@cnr.it

Affiliation:

Istituto Biostrutture e Bioimmagini, Consiglio nazionale delle Ricerche

ORCID:

0000-0003-1004-195X

This project aims to develop suitable methods to track, control and, where required, enhance the delivery of RNA and RNA-targeting drugs in the different cellular compartments. In particular, by combining experimental and computational approaches, several ‘smart’ nanocarriers will be developed and tested for their ability to transport RNA, also labelled with fluorescent probes, on specific targets. The nanocarriers will be decorated with antibodies or other target-specific recognition motifs. The binding to the cellular targets will be monitored using advanced imaging techniques.

We are focused on two types of carriers, nanoparticles of human albumin (NP-HSA) and encapsulating proteins (forming large cages of about 40 nm). We have already developed and patented a technology based on NP-HSA decorated with antibody fragments working as homing and targeting agents for bioactive molecules. NP-HSAs are prepared with an average size of 100 nm, are modified with specific linkers and enzymatically decorated with target-specific antibody fragments. We are also producing, characterising and solving the crystal structure of the encapsulating protein Naplin, which will be modified to enhance RNA encapsulating ability and functionalised with target-specific aptamers from IEOS.

At the same time, we are working on the design and characterization of modified fluorescent nucleobases,
which allow the study of the interaction of the RNA fragments without perturbing their structural behaviour. Our focus will be on thieno modified guanosine analogues, which have already proven very promising performances in DNA. We are now characterizing some new derivatives, which will be prospectively used to make fluorescent the targeting agents or the delivered RNA fragments, enabling their detection and tracking. These ‘smart molecules’, especially in combination with nanocarriers, have a strong applicative potential.

Relevant publications

  1. Sivaccumar J.P. et al., Production in Bacteria and Characterization of Engineered Humanized Fab Fragment Against the Nodal Protein. Pharmaceuticals 2023, 16, 1130

  2. Tkach O, et al., Photophysical characterization of isothiazologuanosine, a unique isomorphic and isofunctional fluorescent analogue of guanosine Journal of Photochemistry and Photobiology A: Chemistry, 2023, 11507

  3. Improta, R Shedding Light on the Photophysics and Photochemistry of I-Motifs Using Quantum Mechanical Calculations. International Journal of Molecular Sciences 2023, 24, 12614

  4. Martinez-Fernandez L. et al, The photophysics of protonated cytidine and hemiprotonated cytidine base pair: A computational study Photochemistry and Photobiology 2023, in press

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