Potential and Challenges of Aptamers as Specific Carriers of Therapeutic Oligonucleotides for Precision Medicine in Cancer

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.

Advances in oligonucleotide drug delivery

“…Similarly, the conjugation of therapeutic oligonucleotides to nucleic acid aptamers (Box 1) has also been explored for enhancing delivery of siRNAs and ASOs to specific target cells 168,195,196 . Aptamers can be considered 'chemical antibodies' that bind to their respective target proteins with high affinity, but present numerous advantages over antibodies as they are simple and inexpensive to manufacture (that is, by chemical synthesis), are smaller in size and exhibit lower immunogenicity 197 .…”

Gene Therapy Options as New Treatment for Inherited Peripheral Neuropathy

“…MMP), cell specific antibodies (e.g. anti-HER2 and anti-CD,3 antibody), and aptamers have been developed to increase the target specificity [ 92 - 94 ]. Thus development of novel specific targets for Schwann cell or peripheral neuron is needed to increase the transfection efficiency of non-viral vectors for IPN gene therapy.…”

Aptamers: a novel targeted theranostic platform for pancreatic ductal adenocarcinoma

“…These PD-1-and PD-L1aptamers could mimic antibody functions in different in- Oligonucleotides, such as microRNAs (miRNAs), miRNA inhibitors (anti-miRs), antisense oligonucleotides (ASOs), and short interfering RNAs (siRNAs), have been shown to potently silence the expression of their target genes. However, one of the most significant obstacles for oligonucleotide-based therapeutic strategies is the lack of specific delivery to the tumor [10]. Aptamers can recognize distinct molecules or structures on cancer cells and get endocytosed quickly upon binding.…”

“…As the selection and generation can be accomplished without structural knowledge of the target molecule, aptamers can also serve as a tool to discover novel biomarkers [9]. Although they were initially conceived and designed as inhibitors, a rising number of studies reports functionally targeted agent delivery systems employing aptamers [10]. Thus, aptamers emerge as promising tools for both diagnostic and therapeutic purposes.…”