# Optimizing Composition and Delivery of a Novel RNA Therapy for Glioblastoma

> **NIH NIH R41** · TERNALYS THERAPEUTICS, INC. · 2022 · $275,766

## Abstract

ABSTRACT
MicroRNAs have a powerful and well described role in the control of biological processes, both in healthy and
pathologic tissue. Yet, their success in gene therapy applications, particularly for cancer, has been very limited
to date. This shortcoming is mainly due to the fact that single microRNA strategies have been implemented. On
the contrary, the promise of microRNAs as a valid therapeutic tool relies on their unique property to function in
clusters, whereby groups of closely associated microRNAs regulate intertwined, and often redundant, cellular
pathways. This oncogenic redundancy is at the base for the failure of many targeted therapies, as it mediates
rescue phenomena responsible for resistance.
Ternalys Therapeutics, Inc., is a startup company based on intellectual property which allows the design and
production of chimeric artificial RNA genes that can simultaneously modulate multiple microRNAs of choice, thus
re-establishing expression of desired microRNA clusters, and achieve precision multitargeting. We have
demonstrated the validity of this approach in glioblastoma, the most lethal and common of brain cancers in the
adult population. This cancer relies on a complex of undruggable chromatin-modifying enzymes to enact
resistance against genotoxic stress and sustain stemness. This complex, and the crucial biologic responses
that it mediates, can be successfully targeted with a combination of multiple microRNAs encoded by recombinant
RNA transgenes of our design.
In this proposal we seek to fine tune the potency and applicability of our product, by pursuing two independent
and correlated specific aims. In Aim 1, three transgenic RNAs with progressively higher microRNA-modulating
capability will be compared for their ability to interfere with the glioblastoma epigenetic landscape, and to
synergize with genotoxic stress provided by standard of care chemoradiation. In Aim 2 we will select a suitable
delivery strategy for the candidate transgene, comparing delivery efficiency between Lentiviral and Adeno-
Associated Virus vectors in a preclinical mouse model of intracranial glioblastoma.
EXPECTED OUTCOME: By the end of Phase I, we will have sufficient data to select the best performing product,
which will then undergo IND-enabling studies in a follow-up Phase II application

## Key facts

- **NIH application ID:** 10603203
- **Project number:** 1R41CA278074-01
- **Recipient organization:** TERNALYS THERAPEUTICS, INC.
- **Principal Investigator:** KENNETH MOCH
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $275,766
- **Award type:** 1
- **Project period:** 2022-09-07 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10603203

## Citation

> US National Institutes of Health, RePORTER application 10603203, Optimizing Composition and Delivery of a Novel RNA Therapy for Glioblastoma (1R41CA278074-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10603203. Licensed CC0.

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