In vitro RNA SELEX for the generation of chemically-optimized therapeutic RNA drugs

Urak, Kevin T.; Shore, Sabrina; Rockey, William M.; Chen, Shi‐Jie; McCaffrey, Anton P.; Giangrande, Paloma H.

doi:10.1016/j.ymeth.2016.03.003

Cited by 29 publications

(16 citation statements)

References 43 publications

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“…DNA aptamers are generated through incubation of the target with the library, which is then amplified with Polymerase Chain Reaction (PCR), thus resulting in a dsDNA (double stranded DNA) library subsequently subjected to strand separation to produce a new ssDNA library for the next selection cycle. On the other side, RNA aptamersare subjected to reverse transcription into dsDNA to enable subsequent RNA transcription [145]. DNA aptamers are inherently more stable and the related manufacturing costs are lower than RNA aptamers [146].…”

Section: Aptamersmentioning

confidence: 99%

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Grieco

Brusco

Licata

et al. 2019

IJMS

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Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia as a consequence of pancreatic β cell loss and/or dysfunction, also caused by oxidative stress. The molecular mechanisms involved inβ cell dysfunction and in response to oxidative stress are also regulated by microRNAs (miRNAs). miRNAs are a class of negative gene regulators, which modulate pathologic mechanisms occurring in diabetes and its complications. Although several pharmacological therapies specifically targeting miRNAs have already been developed and brought to the clinic, most previous miRNA-based drug delivery methods were unable to target a specific miRNA in a single cell type or tissue, leading to important off-target effects. In order to overcome these issues, aptamers and nanoparticles have been described as non-cytotoxic vehicles for miRNA-based drug delivery. These approaches could represent an innovative way to specifically target and modulate miRNAs involved in oxidative stress in diabetes and its complications. Therefore, the aims of this review are: (i) to report the role of miRNAs involved in oxidative stress in diabetes as promising therapeutic targets; (ii) to shed light onto the new delivery strategies developed to modulate the expression of miRNAs in diseases.

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Section: Aptamersmentioning

confidence: 99%

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Grieco

Brusco

Licata

et al. 2019

IJMS

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“…In DNA SELEX, the library is often prepared by PCR products. After 20 rounds of selection, the evolutionary library is sequenced by high-throughput sequencing [ 63 ].…”

Section: Aptamer and Selexmentioning

confidence: 99%

Potential Diagnostic and Therapeutic Applications of Oligonucleotide Aptamers in Breast Cancer

Shaikh

et al. 2017

IJMS

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Breast cancer is one of the most common causes of cancer related deaths in women. Currently, with the development of early detection, increased social awareness and kinds of treatment options, survival rate has improved in nearly every type of breast cancer patients. However, about one third patients still have increased chances of recurrence within five years and the five-year relative survival rate in patients with metastasis is less than 30%. Breast cancer contains multiple subtypes. Each subtype could cause distinct clinical outcomes and systemic interventions. Thereby, new targeted therapies are of particular importance to solve this major clinical problem. Aptamers, often termed “chemical antibodies”, are functionally similar to antibodies and have demonstrated their superiority of recognizing target with high selectivity, affinity and stability. With these intrinsic properties, aptamers have been widely studied in cancer biology and some are in clinical trials. In this review, we will firstly discuss about the global impacts and mechanisms of breast cancer, then briefly highlight applications of aptamers that have been developed for breast cancer and finally summarize various challenges in clinical translation of aptamers.

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“…Each unique sequence contains random bases (20–50 nt) flanked by two conserved primer-binding sites, which are used for the PCR amplification step. During selection, the library is incubated with purified target molecules for a specific time; then, the unbound sequences are eliminated (partitioning step), while the target-bound sequences are isolated and directly amplified by PCR (DNA SELEX) or reverse transcribed to amplifiable cDNA and subsequently transcribed back to RNA using T7 RNA polymerase (RNA SELEX) [ 4 , 5 ]. The PCR products are utilized for the next round of selection.…”

Section: Introductionmentioning

confidence: 99%

Aptamer-Based In Vivo Therapeutic Targeting of Glioblastoma

et al. 2020

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Glioblastoma (GBM) is the most aggressive, infiltrative, and lethal brain tumor in humans. Despite the extensive advancement in the knowledge about tumor progression and treatment over the last few years, the prognosis of GBM is still very poor due to the difficulty of targeting drugs or anticancer molecules to GBM cells. The major challenge in improving GBM treatment implicates the development of a targeted drug delivery system, capable of crossing the blood–brain barrier (BBB) and specifically targeting GBM cells. Aptamers possess many characteristics that make them ideal novel therapeutic agents for the treatment of GBM. They are short single-stranded nucleic acids (RNA or ssDNA) able to bind to a molecular target with high affinity and specificity. Several GBM-targeting aptamers have been developed for imaging, tumor cell isolation from biopsies, and drug/anticancer molecule delivery to the tumor cells. Due to their properties (low immunogenicity, long stability, and toxicity), a large number of aptamers have been selected against GBM biomarkers and tested in GBM cell lines, while only a few of them have also been tested in in vivo models of GBM. Herein, we specifically focus on aptamers tested in GBM in vivo models that can be considered as new diagnostic and/or therapeutic tools for GBM patients’ treatment.

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In vitro RNA SELEX for the generation of chemically-optimized therapeutic RNA drugs

Cited by 29 publications

References 43 publications

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Potential Diagnostic and Therapeutic Applications of Oligonucleotide Aptamers in Breast Cancer

Aptamer-Based In Vivo Therapeutic Targeting of Glioblastoma

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