Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model

Oh, Binna; Song, Hyun-Ok; Lee, Dahee; Oh, Jungju; Kim, Gyeungyun; Ihm, Sung-Hee; Lee, Minhyung

doi:10.1080/1061186x.2016.1207648

Cited by 26 publications

(14 citation statements)

References 22 publications

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“…The amphiphilic R3V6 peptide is a good carrier in vitro and in vivo for the delivery of anti-miR-21 in glioblastoma. The authors recorded low tumor growth following intratumoral injection of the antimiR-21/R3V6 complex, compared with the antimiR-21/PEI25k and scrambled-antisense/R3V6 compounds [104].…”

Section: Peptidesmentioning

confidence: 99%

microRNAs as Novel Therapeutics in Cancer

Romano

Acunzo

Nana‐Sinkam

2021

Cancers

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In the last 20 years, the functional roles for miRNAs in gene regulation have been well established. MiRNAs act as regulators in virtually all biological pathways and thus have been implicated in numerous diseases, including cancer. They are particularly relevant in regulating the basic hallmarks of cancer, including apoptosis, proliferation, migration, and invasion. Despite the substantial progress made in identifying the molecular mechanisms driving the deregulation of miRNAs in cancer, the clinical translation of these important molecules to therapy remains in its infancy. The paucity of vehicles available for the safe and efficient delivery of miRNAs and ongoing concerns for toxicity remain major obstacles to clinical application. Novel formulations and the development of new vectors have significantly improved the stability of oligonucleotides, increasing the effectiveness of therapy. Furthermore, the use of specific moieties for delivery in target tissues or cells has increased the specificity of treatment. The use of new technologies has allowed small but important steps toward more specific therapeutic delivery in tumor tissues and cells. Although a long road remains, the path ahead holds great potential. Currently, a few miRNA drugs are under investigation in human clinical trials with promising results ahead.

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Section: Peptidesmentioning

confidence: 99%

microRNAs as Novel Therapeutics in Cancer

Romano

Acunzo

Nana‐Sinkam

2021

Cancers

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“…AMOs form together with their target miRNAs RNA duplexes which lead to the degradation of miRNAs by RNAse H. In order to function in vivo, AMOs require chemical modifications like 2′-O-methoxyethyl and phosphorothioate. Oh et al showed that by administering anti-miR-21 antisense oligodeoxynucleotide carrier by R3V6 peptide which has amphiphilic properties, directly in the glioblastoma of a xenograft animal model, the apoptosis of tumor cells was restored and consequently tumor growth was blocked [74].…”

Section: Mirnas As Potential Therapeutic Toolsmentioning

confidence: 99%

MicroRNA based theranostics for brain cancer: basic principles

Petrescu

Sabo

Torsin

et al. 2019

J Exp Clin Cancer Res

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Background: Because of the complexity of the blood-brain barrier (BBB), brain tumors, especially the most common and aggressive primary malignant tumor type arising from the central nervous system (CNS), glioblastoma, remain an essential challenge regarding diagnostic and treatment. There are no approved circulating diagnostic or prognostic biomarkers, nor novel therapies like immune checkpoint inhibitors for glioblastoma, and chemotherapy brings only minimal survival benefits. The development of molecular biology led to the discovery of new potential diagnostic tools and therapeutic targets, offering the premise to detect patients at earlier stages and overcome the current poor prognosis. Main body: One potential diagnostic and therapeutic breakthrough might come from microRNAs (miRNAs). It is wellknown that miRNAs play a role in the initiation and development of various types of cancer, including glioblastoma. The review aims to answer the following questions concerning the role of RNA theranostics for brain tumors: (1) which miRNAs are the best candidates to become early diagnostic and prognostic circulating biomarkers?; (2) how to deliver the therapeutic agents in the CNS to overcome the BBB?; (3) which are the best methods to restore/inhibit miRNAs? Conclusions: Because of the proven roles played by miRNAs in gliomagenesis and of their capacity to pass from the CNS tissue into the blood or cerebrospinal fluid (CSF), we propose miRNAs as ideal diagnostic and prognostic biomarkers. Moreover, recent advances in direct miRNA restoration (miRNA mimics) and miRNA inhibition therapy (antisense oligonucleotides, antagomirs, locked nucleic acid anti-miRNA, small molecule miRNA inhibitors) make miRNAs perfect candidates for entering clinical trials for glioblastoma treatment.

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“…In addition to cultured glioma cells [ 87 , 249 ], several studies attempted miR-21 inhibition in established intracranial GBM, using various antagomiRs and delivery techniques. For example, injections of the miR-21 antisense-ODN complex with amphiphilic R3V6 peptide suppressed tumor growth of C6 glioma [ 250 ]. A selective small molecule inhibitor of miR-21 maturation (AC1MMYR2), when injected intraperitoneally to mice bearing orthotopic U87 tumors inhibited tumorigenesis [ 251 ].…”

Section: Microrna Normalization By Otmentioning

confidence: 99%

Oligonucleotide Therapeutics as a New Class of Drugs for Malignant Brain Tumors: Targeting mRNAs, Regulatory RNAs, Mutations, Combinations, and Beyond

Krichevsky

Uhlmann

2019

Neurotherapeutics

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Malignant brain tumors are rapidly progressive and often fatal owing to resistance to therapies and based on their complex biology, heterogeneity, and isolation from systemic circulation. Glioblastoma is the most common and most aggressive primary brain tumor, has high mortality, and affects both children and adults. Despite significant advances in understanding the pathology, multiple clinical trials employing various treatment strategies have failed. With much expanded knowledge of the GBM genome, epigenome, and transcriptome, the field of neuro-oncology is getting closer to achieve breakthrough-targeted molecular therapies. Current developments of oligonucleotide chemistries for CNS applications make this new class of drugs very attractive for targeting molecular pathways dysregulated in brain tumors and are anticipated to vastly expand the spectrum of currently targetable molecules. In this chapter, we will overview the molecular landscape of malignant gliomas and explore the most prominent molecular targets (mRNAs, miRNAs, lncRNAs, and genomic mutations) that provide opportunities for the development of oligonucleotide therapeutics for this class of neurologic diseases. Because malignant brain tumors focally disrupt the blood–brain barrier, this class of diseases might be also more susceptible to systemic treatments with oligonucleotides than other neurologic disorders and, thus, present an entry point for the oligonucleotide therapeutics to the CNS. Nevertheless, delivery of oligonucleotides remains a crucial part of the treatment strategy. Finally, synthetic gRNAs guiding CRISPR–Cas9 editing technologies have a tremendous potential to further expand the applications of oligonucleotide therapeutics and take them beyond RNA targeting.

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Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model

Cited by 26 publications

References 22 publications

microRNAs as Novel Therapeutics in Cancer

microRNAs as Novel Therapeutics in Cancer

MicroRNA based theranostics for brain cancer: basic principles

Oligonucleotide Therapeutics as a New Class of Drugs for Malignant Brain Tumors: Targeting mRNAs, Regulatory RNAs, Mutations, Combinations, and Beyond

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