Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

miRNA-Nanotechnology as a novel regenerative therapy for lymphangioleiomyomatosis

Award Number: R41HG013603
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/25/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2025

Group Awards By:

View Award Description

miRNA-Nanotechnology as a novel regenerative therapy for lymphangioleiomyomatosis - ABSTRACT Lymphangioleiomyomatosis (LAM) is a Tuberous sclerosis-related disorder. Both occur due to an inherited or sporadic mutation in either the TSC1 or TSC2 gene, which function as negative regulators of the mTOR pathway. Uncontrolled mTORC1 activity leads to the neoplastic proliferation of abnormal smooth muscle cells (LAM cells) in the lungs, progressive shortness of breath, recurrent pneumothoraxes, and loss of pulmonary tissue structure and function primarily in women. The first and only FDA-approved treatment for LAM is the immunosuppressant sirolimus, marketed since 2015 by Pfizer. It is the current standard-of-care and acts by inhibiting mTORC1. Sirolimus has several clinical disadvantages, including a considerable number of non- responders, severe adverse events due to its immunosuppressive properties and pregnancy category C, limiting its use in women of childbearing age. Thus, there is a high unmet medical need to develop alternative and safer treatment options for LAM and TS. We have identified treatment with miRNA302b mimics as a potential novel therapy for LAM/TS. Using a murine lung injury model, our collaborator Hao Shen was able to show that non-targeted treatment with miRNA302b mimics as neutral lipid emulsion improved lung function, host recovery, and alveolar epithelial regeneration mice. We also demonstrated a “stalled” AT2-AT1 transdifferentiation state in human LAM, suggesting that impaired AT2 fitness may contribute to loss of alveolar structure. Our goal for this grant is the investigation of pulmonary-epithelium targeted miRNA302b mimic lipid nanoparticles (LNP) efficacy for the treatment of LAM by enhancing AT2 cell regeneration. Aim 1 is composed of in vitro characterization of the miRNA-302b mimic lipid nanoparticle and investigation of several targeting strategies in vivo. Our PI Dr. Jake Brenner will design and construct the nanoparticles in his bioengineering lab. We will perform 3D organoid experiments with human and mouse AT2 cells in the presence of the LNP[miR302b] followed by an in vivo study comparing different targeting strategies to reach the desired tissue and cell type using a transgenic model of LAM, developed by our other PI Prof. Vera Krymskaya. Using the most effective targeting strategy, Aim 2 will be an in vivo proof-of-concept study using that same transgenic murine model pre and post-pregnancy to answer the question whether our treatment will prevent airspace enlargement and lead to lung recovery. We will observe mice for 4 and 8 weeks after intratracheal LNP[miR302b] administration. Endpoints will include lung function, BALF analysis, qPCR, and histological lung sections stained for the disease related markers and cell types. All collaborators are experts in their respective field and thus well equipped to successfully complete this project, bringing together a number of unique and innovative aspects to treat this devastating rare disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$39,762 )
2026	2023	BIOSPUTNIK LLC	504 GRAND ST APT D65	NEW YORK	NY	10002	NEW YORK	USA	Human Genome Research	000	1	3/5/2026	NEW	-$39,762
														Subtotal = -$39,762

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	BIOSPUTNIK LLC	504 GRAND ST	NEW YORK	NY	10002	NEW YORK	USA	Human Genome Research	000	1	4/8/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $301,016 )
2023	2023	BIOSPUTNIK LLC	504 GRAND ST	NEW YORK	NY	10002	NEW YORK	USA	Human Genome Research	000	1	9/25/2023	NEW	$301,016
														Subtotal = $301,016

Grand Total All Awards = $261,254

Top

All Categories

About

Search

Reports

Data Submission

Award Information

miRNA-Nanotechnology as a novel regenerative therapy for lymphangioleiomyomatosis

Award Number: R41HG013603

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/25/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer