Aptamers as Theragnostic in Human Diseases


Geroloma Condorelli




Università di Napoli Federico II



Nucleic acid-based aptamers are oligonucleotides which, by virtue of their ability to fold into peculiar 3D architectures, recognize their targets with high affinity and specificity. This project aims to develop innovative nucleic acid-based aptamers as therapeutics and drug carriers in the form of aptamer-drug conjugates/complexes to enhance specificity and decrease off-target effects of drugs.
The development of clinically effective therapeutic aptamers will be achieved by introducing suitable chemical modifications or conjugations into the oligonucleotide backbone of the aptamers, that will enhance their biological activity and resistance against nuclease degradation.
Apart from acting as therapeutics by themselves, aptamers have also a huge potential as drug carriers in the form of aptamer-drug conjugates/complexes, useful for the in vivo delivery of both small molecules and nucleic acid-based drugs, such as siRNA or miRNA.
Within this project we will focus, among others, on aptamers recently identified in prof. Condorelli’s lab: A40s recognizing EphA2 in Glioblastoma cancer stem cells, Ex50.T recognizing breast cancer extracellular vehicles (EV) as well as breast cancer cells, RC.1 recognizing rectal cancer cells and EV, and new aptamers that we are selecting toward NCCLC and pancreatic cancer.
To obtain clinically effective therapeutics, aptamers will be characterized for their high affinity and specificity to the target and their stability in biological environment. Since natural RNA and DNA are susceptible to endogenous nucleases, appropriate chemical modifications will be introduced to improve both pharmacokinetic and pharmacodynamic properties. Our purpose is to introduce proper chemical modifications on the sugar/base moiety and/or phosphodiester backbone of the aptamers or conjugate them with functional molecules at the ends with the aim to improve general aptamer properties. We will obtain the desired information on the conformation and stability of a mini-library of novel modified A40s-based aptamers through biophysical methodologies (NMR, CD, UV-vis, fluorescence spectroscopy and native PAGE analysis). The modified aptamers will then be studied for their interaction with the target protein by biophysical techniques, such as SPR, and for their biological activity in glioblastoma cells, compared to the parent aptamer.

The main activities include:– Design, synthesis and characterization of new therapeutic aptamers.- Development of aptamers conjugated with antisense RNA (RNAi) or microRNA to modify gene expression and interfere with cell transformation pathways and target the tumor microenvironment.- Biophysical studies of the aptamers to characterize their stability and their recognition of the target to reveal the thermodynamic and kinetic aspects of interactions.- Validation of the safety and functional/therapeutic efficacy of the novel designed aptamers both in vitro (cell lines, primary cells, human iPS), in 3D models (organoids) and in vivo (proof of principle).- Study of the pathways regulated by aptamers thought omics approaches.

Relevant publications

  1. Mironov V, Shchugoreva IA, Artyushenko PV, Morozov D, Borbone N, Oliviero G, Zamay TN, Moryachkov RV, Kolovskaya OS, Lukyanenko KA, Song Y, Merkuleva IA, Zabluda VN, Peters G, Koroleva LS, Veprintsev DV, Glazyrin YE, Volosnikova EA, Belenkaya SV, Esina TI, Isaeva AA, Nesmeyanova VS, Shanshin DV, Berlina AN, Komova NS, Svetlichnyi VA, Silnikov VN, Shcherbakov DN, Zamay GS, Zamay SS, Smolyarova T, Tikhonova EP, Chen KH, Jeng US, Condorelli G, de Franciscis V, Groenhof G, Yang C, Moskovsky AA, Fedorov DG, Tomilin FN, Tan W, Alexeev Y, Berezovski MV, Kichkailo AS. Structure and Interaction Based Design of Anti-SARS-CoV-2 Aptamers. Chemistry. 2022 Jan 13. doi: 10.1002/chem.202104481. Online ahead of print.Chemistry. 2022. PMID: 35025110


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PI: Francesco Ricci