# Intranasal Delivery of Telomerase Reverse Transcriptase mRNA for Therapy ofTraumatic Brain Injury

> **NIH NIH R21** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2022 · $444,125

## Abstract

ABSTRACT
It is estimated that annually ~3 million Traumatic brain injury (TBI) cases occur in the U.S. Moderate to severe
TBI can cause significant impairments in mental and motor functions or death. There are no effective
therapies to improve cognitive abilities after moderate-severe TBI. Many novel pharmacological approaches for
TBI therapy are not effective enough. Gene therapy can provide an unmet solution in protecting against several
neurodegenerative disorders, including TBI. Recent advances in mRNA therapeutics/ vaccines have drawn
significant attention due to their ability to tackle unmet clinical needs. For instance, the prompt development of
COVID-19 mRNA vaccines aided in controlling the pandemics worldwide. Efficient mRNA therapies require a
Lipid Nanoparticles (LNP) carrier to protect mRNA from degradation. Telomeres, repetitive non-coding DNA
sequences, have a pivotal role in tissue repair and aging. Telomere shortening in the brain results from blood
flow impairment and cell-death related inflammation and affects tissue regeneration ability. A catalytic subunit of
telomerase, an enzyme responsible for maintaining telomere length (TL) during cell division, is telomerase
reverse transcriptase (TERT). TL dysfunction has been implicated in neuroinflammatory and neurodegenerative
processes and proposed as a marker for TBI outcomes. Additionally, TERT was shown to be important in
neuronal survival and cognition, protecting from oxidative stress and blocking neuronal apoptosis. While TERT
is a potential target in neurological disorders, no studies evaluating RNA therapy to address TL in TBI were
reported yet. Here we propose a transformational therapeutic approach for TBI therapy which includes intranasal
(IN) TERT mRNA- LNP delivery to the brain. LNP protect mRNA en route to the target TBI tissue. The immediate
focus of our work is an impairment in the brain's normal function caused by an impact to the head. Our data
show that IN delivery of LNP bypasses BBB, enhancing drug transport to the brain. Our teams have
demonstrated that TERT mRNA can enhance TL in vitro and in vivo improving prognosis in other degenerative
conditions. We have also shown that there is a shortening of telomeres and reduction in TERT levels in our TBI
mouse model.
Our approach may radically change therapy for TBI, as well as other brain disorders. In this
exploratory project, our central hypothesis is that IN administration of TERT mRNA will enable temporary
expression of TERT in the affected brain tissue restoring cognitive functions after TBI. Our Specific aims are:
(1) Design, characterization, and biocompatibility of mRNA-LNP in vitro: four TERT-mRNA-LNP systems will be
designed, characterized, and assessed in vitro with various brain cells; (2) Evaluate the biodistribution and
therapeutic efficiency of IN administration of TERT mRNA-LNPs in a mouse model of TBI (Controlled cortical
impact, CCI). Biodistribution of reporter mRNA and fluorescently labeled LNP ...

## Key facts

- **NIH application ID:** 10602034
- **Project number:** 1R21NS127265-01A1
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Biana Godin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $444,125
- **Award type:** 1
- **Project period:** 2022-09-26 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10602034

## Citation

> US National Institutes of Health, RePORTER application 10602034, Intranasal Delivery of Telomerase Reverse Transcriptase mRNA for Therapy ofTraumatic Brain Injury (1R21NS127265-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10602034. Licensed CC0.

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