RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review

Our plain-English summary of RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review, by E. Generalov, A. Shevelev, D. Romanov, et al (Pharmaceutics, 2026).

The study

• Authors: E. Generalov, A. Shevelev, D. Romanov, O. Tarasova, N. Pozdniakova
• Journal: Pharmaceutics
• Published: 2026;18(4)
• Type of article: Review
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: RNA therapeutics represent a rapidly advancing field with significant potential for treating viral infections and cancer. This review examines the current landscape of RNA-based strategies, including siRNA, miRNA mimics, and antisense oligonucleotides. For viral infections, the focus is on hepatitis B (HBV) and C (HCV), HIV, and SARS-CoV-2. Approaches include targeting viral transcripts directly (e.g., siRNAs against HBV surface antigen) or host factors critical for viral replication (e.g., anti-miR-122 miravirsen for HCV). The successful development of mRNA vaccines for COVID-19 is highlighted as a major breakthrough, demonstrating the feasibility of rapid RNA vaccine deployment. The manuscript reviews several RNA therapeutics in oncology that have reached clinical trials. These include TargomiR (a miR-16 mimic for mesothelioma), cobomarsen (an anti-miR-155 for lymphomas), and MRX34 (a miR-34a mimic for various solid tumours). The review also covers emerging candidates like an miR-221 inhibitor and various strategies for breast cancer, such as targeting Bcl-2, KRAS, and specific miRNAs. A critical challenge across both fields is developing efficient and safe delivery systems, including lipid nanoparticles, GalNAc conjugates, and bacterial minicells. Despite promising preclinical results, clinical translation has been hampered by issues like insufficient delivery efficiency to human tumours, toxicity, and the complex, interconnected regulatory networks of miRNAs, which can lead to unpredictable off-target effects. Conclusions: While RNA therapeutics hold immense promise, overcoming delivery barriers and enhancing understanding of RNA regulatory networks are essential for future success.

In plain English

This was a narrative review of RNA-based therapeutics for viral infections and cancer, covering siRNA, miRNA mimics and inhibitors, antisense oligonucleotides and mRNA vaccines, together with delivery systems such as lipid nanoparticles, GalNAc conjugates and bacterial minicells. For hepatitis C, the authors described a Phase IIa trial of miravirsen (anti-miR-122) in 36 patients with chronic genotype 1 infection, in which trial organisers observed no side effects requiring dose limitation and no mutations in miR-122 binding sites. In oncology, they reported that Phase I testing of TargomiR, a miR-16 mimic carried in bacterial minicells for malignant pleural mesothelioma and non-small cell lung cancer, was run in Australia between 2014 and 2017 in 27 patients and was discontinued in 2017; that a Phase I trial of the miR-34a mimic MRX34 enrolled 48 adult patients with advanced solid tumours, including 14 with hepatocellular carcinoma, with fever in 64% and fatigue in 57%; and that of 16 assessable patients given LNA-i-miR-221, 8 had stable disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of RNA-based drugs (siRNA, miRNA mimics and inhibitors, antisense oligonucleotides, mRNA vaccines) in viral infections and cancer
• Who was studied: Published preclinical and clinical studies of selected RNA-based therapeutic agents, chosen mainly because they had reached Phase I/II trials or targeted well-characterised oncogenic or viral pathways; indications included hepatitis B and C, HIV, SARS-CoV-2, malignant pleural mesothelioma, lymphomas and leukaemias, liver cancer, melanoma and breast cancer
• Exposure: RNA therapeutic classes (siRNA, miRNA mimics, miRNA inhibitors, antisense oligonucleotides, mRNA and self-amplifying RNA vaccines) and their delivery vehicles (lipid nanoparticles, GalNAc conjugates, bacterial minicells)
• Main results:
  • Phase I testing of TargomiR (miR-16 mimic in bacterial minicells) for malignant pleural mesothelioma and non-small cell lung cancer involved 27 patients in Australia, 2014-2017; the authors stated the results were deemed unsatisfactory and the trial was discontinued in 2017
  • The Phase I trial of MRX34 (liposomal miR-34a mimic) enrolled 48 adult patients with treatment-resistant solid tumours, of whom 14 had hepatocellular carcinoma
  • Most common side effects reported in the MRX34 Phase I patients
  • In the MRX34 Phase I trial, the maximum tolerated dose for patients without HCC was 110 mg/m2, with hypoxia and enteritis reported in two patients at higher doses
  • One patient with HCC in the MRX34 Phase I trial had a durable confirmed response at 48 weeks, but the trial was discontinued in 2016 because efficacy results were considered unsatisfactory
  • In a Phase IIa trial of miravirsen (anti-miR-122) at seven centres in 36 patients with chronic HCV genotype 1 infection, no dose-limiting side effects and no mutations in miR-122 binding sites were observed
  • Among patients with refractory advanced cancer given the miR-221 inhibitor LNA-i-miR-221 whose response could be assessed, 8 of 16 had stable disease
  • For cobomarsen (anti-miR-155), Phase II was terminated in 2020, and the authors proposed the terminations reflected sponsor business decisions rather than toxicity or lack of efficacy
  • For the SARS-CoV-2 mRNA vaccines, the authors reported developers' claims of 95% protection against infection, versus 48% protection when uracil was not replaced with 1m-pseudouridine
• The authors' conclusion: The authors concluded that mRNA vaccines against SARS-CoV-2 showed RNA's potential, but that frequent discontinuation of early-phase cancer trials shows therapeutic potential depends on overcoming delivery barriers and systemic toxicity, with safe and specific delivery systems the primary technical challenge
• Limitations the authors state:
  • The authors state that long-term side effects of RNA therapeutics remain insufficiently studied because follow-up has been short
  • The authors state that the complexity of miRNA, mRNA and long non-coding RNA networks makes the whole-organism consequences of miRNA mimics and inhibitors very hard to predict
  • The authors state that for cobomarsen the efficiency of delivery of the active substance in humans was not evaluated in the clinical trials, so their explanation for its failure is an assumption

Topics

Medical terms in this study, explained in our Lexicon: Clinical Trial, Mesothelioma.

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