Utilizing RNA Replicons as Immune Modulators for Systemic Lupus Erythematosus

A self-replicating RNA platform delivers anti-inflammatory cytokines directly to the airways, offering targeted local immune suppression without systemic toxicity — a mechanistically distinct approach to treating lupus lung disease.
Complete Autoimmune-Associated Interstitial Lung Disease Other Pulmonary & Cardiovascular Diseases Systemic Diseases Systemic Lupus Erythematosus (SLE) Adaptive Immunity Animal Models Biological & Mechanistic Cytokine Signaling Drug Repurposing Experimental Platforms & Models In Vitro Models Innate Immunity Precision Medicine Therapeutic Development Translational & Clinical

Funding Year: 2023

Project Overview

Systemic lupus erythematosus (SLE) is a serious autoimmune disease in which the immune system attacks the body's own tissues, with the lungs particularly vulnerable to life-threatening complications. Current treatments broadly suppress immunity, raising infection risk and limiting their long-term tolerability. This project explores a targeted alternative using a self-replicating RNA delivery system developed at NYU, capable of delivering anti-inflammatory cytokines — specifically IL-10 and TGF-β — directly to the airways to calm local immune responses without systemic suppression. Early lab studies confirmed the platform's safety across a wide dose range in wild-type mice, with peak expression at 28 hours and natural decline within one week. Delivery of IL-10 or TGF-β in lupus mouse models significantly reduced T and B cell infiltration in the lungs, demonstrating meaningful therapeutic potential without global immune suppression.

Impact & Innovation

Targeted relief, without systemic suppression.

 

This project delivers a self-replicating RNA platform that calms lung inflammation in lupus mouse models without broad immunosuppression — and has already advanced to FDA pre-IND review.

  • Addresses a critical limitation of current SLE therapies: the inability to modulate immune activity locally without compromising systemic immunity
  • Confirmed the platform delivers anti-inflammatory cytokines locally without triggering innate immune responses — with a provisional patent filed
  • Advances the Consortium’s From Mechanistic Insight to Translation pillar, from preclinical validation to active FDA pre-IND review
Research Approach

A framework designed for discovery

This project combined RNA engineering, in vivo safety testing, and autoimmune disease modeling to develop and validate a self-replicating RNA delivery platform for targeted immune modulation in SLE. The work progressed from platform construction and safety characterization through therapeutic efficacy testing in preclinical lupus models.

Generation of self-replicating RNAs encoding IL-10 and TGF-β for intranasal delivery; in vivo safety and expression profiling in wild-type mice across a wide dose range; and therapeutic efficacy testing via intranasal delivery in lupus mouse models, with assessment of lung immune cell infiltration and systemic immune effects.

Wild-type mouse safety and expression datasets, lupus mouse models treated with IL-10 or TGF-β via the RNA replicon platform, and immune infiltration readouts (T and B cell populations) in lung tissue to assess local vs. systemic immune modulation.

Validation of the RNA replicon platform as a safe, targeted, and controllable delivery system for localized cytokine therapy in autoimmune lung disease, with translational steps including a pre-IND FDA submission and a pending clinical expansion grant. Peer-reviewed publication is anticipated within one to two years pending completion of additional studies.

Investigators & Institutions

Powering the science

Principal Investigator

Benjamin tenOever, PhD, Colton Consortium Member

NYU Grossman School of Medicine

Colton Centers & Institutions

Judith & Stewart Colton Center for Autoimmunity at NYU Langone Health

NYU Grossman School of Medicine

Research Outputs

From insight to impact

Grant application pending to expand studies into a clinical setting.

U.S. Provisional Application No. 63/472,205: RNA-based immune modulation platform. Pre-IND submission to the FDA currently under review to support clinical translation. (filed June 9, 2023)