# Advanced tools for translation of intravenously-infused RNA LNP therapeutics to the clinic

> **NIH NIH R44** · REJUVENATION TECHNOLOGIES, INC. · 2024 · $520,303

## Abstract

Abstract
Rejuvenation Technologies Inc. (RTI) seeks to improve the tools required for clinical translation of intravenously-
infused RNA lipid nanoparticle (LNP) therapeutics. While there is abundant work on RNA LNP vaccines, the
requirements for intravenously-infused LNPs are significantly more demanding, because instead of causing an
immune response as with a vaccine, IV-infused LNPs must avoid an immune response. Immune responses can
be caused by the RNA or the LNP components, and can lead to adaptive immunity, autoimmunity, anaphylactic
shock, desensitization or sensitization, and reduced drug potency with repeat dosing. As a test case, RTI will
focus on their telomere extension biologic, which has shown highly successful proof-of-concept rescue of
multiple mouse models of liver and lung disease. Telomeres are the protective DNA tips of chromosomes.
Telomeres shorten with each cell division, eventually exposing the DNA tip, causing genome instability and
progenitor cell apoptosis or senescence. This diminishes the regenerative capacity of organs, driving a number
of pathological conditions that include aging-related diseases like lung, kidney, and liver fibrosis, and bone
marrow failure. Thus, telomere extension represents a promising strategy for regenerative medicine. RTI’s
solution is to extend critically short telomeres by transiently increasing TERT levels via targeted delivery of
modified TERT mRNA in biodegradable lipid nanoparticles (LNPs). RTI has multiple LNPs capable of delivering
mRNA to the lung or liver with world- leading efficiency, transfecting >90% of target cells, even in diseased
organs. Upon delivery to cells, TERT mRNA is translated to functional TERT protein, and both are degraded
within days, yet telomeres are extended sufficiently to reverse years of shortening. Preliminary work has shown
the strong potential benefits of the TERT therapy in models of both liver and lung fibrosis. Moreover, RTI has
developed broadly transfecting-LNPs capable of transfecting 16 tissues in non-human primates, opening the
door to extra-hepatic extra-pulmonary mRNA delivery. In the future, RTI intends to add targeting ligands,
conferring additional cell type-specificity and enabling the extension of these results to other forms of disease.
In this Direct to Phase II project, RTI seeks to develop a platform that can be used for efficient translation and
manufacturing following FDA’s chemistry, manufacturing, and controls guidelines of TERT mRNA LNP therapies
from preclinical models to the clinic. To do so, RTI will undertake four specific aims: 1) high-sensitivity drug-
specific analytical capability development, 2) high-sensitivity cell-type-specific biodistribution, 3) evaluating drug
component stability, and 4) high-sensitivity bioanalytical methods for identifying drug breakdown products. These
studies will provide the high-sensitivity methods critical for clinical translation of intravenously-infused RNA LNP
therapeutic drug products. ...

## Key facts

- **NIH application ID:** 11008472
- **Project number:** 1R44TR005328-01
- **Recipient organization:** REJUVENATION TECHNOLOGIES, INC.
- **Principal Investigator:** John Ramunas
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $520,303
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-09-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008472

## Citation

> US National Institutes of Health, RePORTER application 11008472, Advanced tools for translation of intravenously-infused RNA LNP therapeutics to the clinic (1R44TR005328-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11008472. Licensed CC0.

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