Abstract

Due to the progress made in the area of precision and personalized medicine in the field of cancer therapy, strategies to selectively and specifically identify target molecules causative of the diseases are urgently needed. Efforts are being made by a number of different laboratories, companies, and researchers to develop therapeutic molecules that selectively recognize the tissues and the cells of interest, exhibit few or no off-target and side effects, are non-immunogenic, and have a strong action. Aptamers, artificially selected single-stranded DNA or RNA oligonucleotides, are promising molecules satisfying many of the requirements needed for diagnosis and precision medicine. Aptamers can also couple to their native mechanism of action the delivery of additional molecules (oligonucleotides, siRNAs, miRNAs) to target cells. In this review, we summarize recent progress in the aptamer-mediated strategy for the specific delivery of therapeutic oligonucleotides.

Highlights

  • The development of oligonucleotides for therapeutics started two decades ago [1]

  • Ramezanpour M et al demonstrated a synergic effect in gastric cancer cells of a chimera consisting of nucleolin-specific aptamer (NCL-Apt) and the miRNA let-7d on JAK2 expression [57]

  • In 2018, Zhu et al targeted viral NSP9 with short antisense oligonucleotides (ASOs) composed from locked nucleic acids (LNAs), which have a methylene linkage between 20 -O and 40 -C of the sugar ring, This modification led to increased thermostability and resistance to nucleases, allowing improved inhibition of porcine reproductive and respiratory syndrome [72]

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Summary

Introduction

The development of oligonucleotides for therapeutics started two decades ago [1]. Nowadays the treatment of many gene-specific diseases can take advantage of the use of a plethora of oligonucleotides such as microRNAs (miRNAs), miRNA inhibitors (anti-miRs), antisense oligonucleotides (ASOs), and short interfering RNAs (siRNAs). RNA aptamers form more three‐dimensional structures, and due to the strong RNA‐RNA interaction, aptamers when used in vivo are degraded by nuclease digestion. To overcome they show a high conformation stability [9]. Purines with if all all thethe pyrimidines are 2modified with 2′‐fluoro chemistry and all the purines with 2′‐O methyl [12] Due to to their their tridimensional tridimensional structure, structure, aptamers aptamers bind bind specific specific targets targets with with high high specificity specificity and and.

Aptamers
Aptamers as Carriers for siRNAs
Schematic
Aptamers as Carriers for shRNAs
Aptamers as Carriers for ASOs
Conclusions
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