Simultaneous Targeting of Multiple oncomiRs with Phosphorothioate or PNA-Based Anti-miRs in Lymphoma Cell Lines

Dhuri, Karishma; Pradeep, Sai Pallavi; Shi, Jason; Anastasiadou, Eleni; Slack, Frank J.; Gupta, Anisha; Zhong, Xiao‐bo; Bahal, Raman

doi:10.1007/s11095-022-03383-y

Cited by 5 publications

(7 citation statements)

References 44 publications

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“…Co-targeting two oncomiRs (miR-21 and miR-155) in lymphoma cell lines using PNAs and another anti-miR oligonucleotide called phosphorothioates (PS) has shown significant knockdown of the target miRNAs and reduced cell viability in lymphoma cells [ 147 ]. By substituting one non-bridging oxygen of the oligonucleotide with a hydrophobic sulfur atom, phosphorothioate, increases the stability as well as the availability of the nucleotide, thus making it a promising tool for therapeutics [ 148 , 149 ].…”

Section: Mirna Therapeuticsmentioning

confidence: 99%

miRNA: A Promising Therapeutic Target in Cancer

Menon

Abd‐Aziz

Khalid

et al. 2022

IJMS

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microRNAs are small non-coding RNAs that regulate several genes post-transcriptionally by complementarity pairing. Since discovery, they have been reported to be involved in a variety of biological functions and pathologies including cancer. In cancer, they can act as a tumor suppressor or oncomiR depending on the cell type. Studies have shown that miRNA-based therapy, either by inhibiting an oncomiR or by inducing a tumor suppressor, is effective in cancer treatment. This review focusses on the role of miRNA in cancer, therapeutic approaches with miRNAs and how they can be effectively delivered into a system. We have also summarized the patents and clinical trials in progress for miRNA therapy.

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Section: Mirna Therapeuticsmentioning

confidence: 99%

miRNA: A Promising Therapeutic Target in Cancer

Menon

Abd‐Aziz

Khalid

et al. 2022

IJMS

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“…We also evaluated the antisense activity of PS and PNA based oligomers to inhibit multiple oncomiRs. Both PS and PNA ASOs when delivered via PLGA NPs showed comparable inhibition of miR-155 (~90%) and miR-21 (~50%) in lymphoma cells 54 . Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors with high recurrence rate and dismal survival.…”

Section: Antimir Pnasmentioning

confidence: 99%

“…Prior studies have established the role of oncomiRs-155 and -21 in driving tumorigenesis in B-cell lymphoma. Hence, we utilized antimiR PNAs delivered via PLGA NPs to inhibit both oncomiRs-155 and -21 together, which showed an ~80% reduction in viability of lymphoma cells compared to the single treatments (~50%) 54,55 . We also evaluated the antisense activity of PS and PNA based oligomers to inhibit multiple oncomiRs.…”

Section: Antimir Pnasmentioning

confidence: 99%

Unlocking the potential of chemically modified peptide nucleic acids for RNA-based therapeutics

Pradeep

Malik

Slack

et al. 2023

RNA

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RNA therapeutics have emerged as next-generation therapy for the treatment of many diseases. Unlike small molecules, RNA targeted drugs are not limited by the availability of binding pockets on the protein, but rather utilize Watson crick (WC) base pairing rules to recognize the target RNA and modulate gene expression. Antisense oligonucleotides (ASOs) present a powerful therapeutic approach to treat disorders triggered by genetic alterations. ASOs recognize the cognate site on the target RNA to alter gene expression. Nine single-stranded ASOs have been approved for clinical use and several candidates are in late-stage clinical trials for both rare and common diseases. Several chemical modifications including phosphorothioates, locked nucleic acid, phosphorodiamidate, morpholino, and peptide nucleic acids (PNAs) have been investigated for efficient RNA targeting. PNAs are synthetic DNA mimics where the deoxyribose phosphate backbone is replaced by N-(2-aminoethyl) glycine units. The neutral pseudopeptide backbone of PNAs contributes to enhanced binding affinity and high biological stability. PNAs hybridize with the complementary site in the target RNA and act by a steric hindrance-based mechanism. In the last three decades various PNA designs, chemical modifications, and delivery strategies have been explored to demonstrate their potential as an effective and safe RNA-targeting platform. This review covers the advances in PNA-mediated targeting of coding and non-coding RNAs for a myriad of therapeutic applications.

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“… 64 Intratumoral U2932 cell line-derived xenograft mice Decreased miR-155 expression, reduced tumor growth miR-21, miR-155 Anti-miR-21 PNA PLGA NPs, anti-miR-155 PNA PLGA NPs Cellular transfection U2932, SUDHL-5, and SUDHL-2 cell lines Decreased miR-155 expression, decreased cell viability Dhuri et al. 65 Cervical cancer miR-210 22-mer γPNA, encapsulated with PLGA NPs Decreased miRNA-mRNA interaction Intratumoral HeLa tumor xenograft mice Decreased miR-210 expression, decreased tumor growth, improved tumor morphology and histopathology Gupta et al. 32 …”

Section: Antisense Applications As Anti-cancer Agentsmentioning

confidence: 99%

Therapeutic and diagnostic applications of antisense peptide nucleic acids

MacLelland,

Kravitz,

Gupta

2024

Molecular Therapy - Nucleic Acids

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Simultaneous Targeting of Multiple oncomiRs with Phosphorothioate or PNA-Based Anti-miRs in Lymphoma Cell Lines

Cited by 5 publications

References 44 publications

miRNA: A Promising Therapeutic Target in Cancer

miRNA: A Promising Therapeutic Target in Cancer

Unlocking the potential of chemically modified peptide nucleic acids for RNA-based therapeutics

Therapeutic and diagnostic applications of antisense peptide nucleic acids

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