---
title: "Bioengineered microRNAs (miR-124, miR-34a) sensitize high-risk neuroblastoma to cisplatin"
id: "biorxiv-23-synergistic-combination-of-bioengineered-microrna-and-chemotherapy-across-high"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-23-synergistic-combination-of-bioengineered-microrna-and-chemotherapy-across-high"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1?rss=1"
published_at: "2026-10-02T11:00:56.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Bioengineered microRNAs (miR-124, miR-34a) sensitize high-risk neuroblastoma to cisplatin
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-23-synergistic-combination-of-bioengineered-microrna-and-chemotherapy-across-high
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1?rss=1)
- **Published At:** 2026-10-02T11:00:56.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- High-risk neuroblastoma (HRNB) remains a leading cause of pediatric cancer mortality despite multimodal and multi-agent chemotherapy; platinum drugs like **cisplatin** are central to therapy but cause significant acute and long-term toxicities. - MicroRNA-based therapeutics can target multiple oncogenic pathways simultaneously; conventional chemically synthesized miRs face inconsistency and poor in vivo stability. - The authors used biologically produced, tRNA/pre-miR containing bioengineered microRNAs (**bioRNA**) encoding **miR-124** and **miR-34a** to address manufacturing and stability limitations. - In vitro, both **bioRNA** constructs significantly reduced neuroblastoma cell viability across molecularly distinct HRNB models. - Proteomic analyses indicated **miR-124** preferentially induced neuronal differentiation programs, while **miR-34a** preferentially activated apoptotic signaling pathways. - Combining either **bioRNA** with **cisplatin** produced robust synergy across multiple HRNB cell lines, increasing apoptosis and promoting differentiation-associated phenotypes. - In vivo xenograft studies showed both **bioRNAs** suppressed tumor growth as monotherapies; the strongest anti-tumor responses occurred when **bioRNA** was combined with low-dose **cisplatin** across different HRNB subtypes. - Notably, low-dose **cisplatin** plus **bioRNA** frequently achieved tumor control comparable to or greater than high-dose **cisplatin** monotherapy while maintaining favorable tolerability in the models used. - The data support **bioRNA** molecules as potent **cisplatin** sensitizers and suggest bioRNA-based combination therapy could improve HRNB outcomes and enable chemotherapy dose reduction to limit toxicity in children. - This work is reported as a preprint and has not been peer-reviewed; full methodological details and data are provided in the source but peer review status should be considered when interpreting findings.
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Yunyoung Lee University of California, Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yunyoung%2BLee%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Lee%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYunyoung%2BLee%2B) Albatool AlKhazal University of California, Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Albatool%2BAlKhazal%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=AlKhazal%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAlbatool%2BAlKhazal%2B) Kathleen E Doyle University of California, Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Kathleen%2BE%2BDoyle%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Doyle%20KE&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AKathleen%2BE%2BDoyle%2B) Yu-Rim Ahn University of California, Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yu-Rim%2BAhn%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Ahn%20Y&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AYu-Rim%2BAhn%2B) Ana Maria Sandoval Castellanos University of California, Davis * [Find this author on Google 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tab") Erin G Brown University of California, Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Erin%2BG%2BBrown%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Brown%20EG&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AErin%2BG%2BBrown%2B) * [ORCID record for Erin G Brown](http://orcid.org/0000-0003-4381-1850 "Open in new tab") * For correspondence: egbrown@health.ucdavis.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5833732/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5833732/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5833732/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5833732/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5833732/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Despite intensive treatment, high-risk neuroblastoma (HRNB) remains a leading cause of cancer-related mortality in children. Current treatment paradigms include multimodal systemic treatments and multi-agent chemotherapy, which is limited by substantial acute and long-term toxicities. Platinum-based chemotherapy is a cornerstone of this treatment but is fraught with side effects and stands to benefit from dose reduction strategies. MicroRNA (miR)-based therapeutics represent an attractive strategy to simultaneously moderate multiple oncogenic pathways, providing a potential avenue to enhance the efficacy of current treatment regimens. However, the development of miR therapeutics has largely relied on chemically synthesized ones, which are limited by issues of inconsistency and poor in vivo stability. Biologically produced, tRNA/pre-miR containing bioengineered miRs (bioRNAs) address these limitations. We investigated the therapeutic potential of bioRNA encoding miR-124 and miR-34a across molecularly distinct HRNB models and evaluated their ability to enhance cisplatin efficacy. Both bioRNAs significantly suppressed neuroblastoma cell viability in vitro, with proteomic analyses demonstrating preferential induction of neuronal differentiation by miR-124 and apoptotic signaling by miR-34a. Combining bioRNA with cisplatin produced robust synergy across multiple HRNB lines, enhancing apoptosis while simultaneously promoting differentiation-associated phenotypes. In vivo, both bioRNAs suppressed tumor growth as monotherapies, while combination with low-dose cisplatin produced the strongest responses across multiple xenograft models with different HRNB subtypes. Notably, low-dose cisplatin combined with bioRNA therapy frequently achieved tumor control comparable to, or greater than, that observed with high-dose cisplatin monotherapy while maintaining favorable tolerability. These findings establish bioRNAs as potent cisplatin sensitizers and support bioRNA-based combination therapy as a strategy for improving HRNB treatment while reducing chemotherapy-associated toxicity in children. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared Hartwell Foundation, SP0A242412 American Pediatric Surgical Association, A25-0973 National Institute of Health, P30CA093373 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/02/2026.09.30.755443.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.09.30.755443v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Synergistic Combination of Bioengineered MicroRNA and Chemotherapy Across High-Risk Neuroblastoma Subtypes Yunyoung Lee, Albatool AlKhazal, Kathleen E Doyle, Yu-Rim Ahn, Ana Maria Sandoval Castellanos, Mei-Juan Tu, Ai-Ming Yu, Jinhwan Kim, Erin G Brown bioRxiv 2026.09.30.755443; doi: https://doi.org/10.64898/2026.09.30.755443 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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