Colton Center for RNA Exploration in Autoimmune Therapeutics (CREATE)

Developing next-generation mRNA-LNP therapeutics that selectively modulate or deplete pathogenic immune cells to treat type 1 diabetes, lupus, multiple sclerosis, and other severe autoimmune conditions.
Ongoing Endocrine Diseases Multiple Sclerosis Neurologic Diseases Systemic Diseases Systemic Lupus Erythematosus (SLE) Type 1 Diabetes Animal Models Biological & Mechanistic Clinical Trials Experimental Platforms & Models Immune Tolerance In Vitro Models Precision Medicine T Cell Biology Therapeutic Development Translational & Clinical

Funding Year: 2025

Project Overview

CREATE harnesses Penn's RNA and cell therapy infrastructure to develop non-inflammatory, targeted mRNA-LNP constructs manufactured under GMP conditions for complex autoimmune diseases. The center is pioneering three novel therapeutic categories: adjuvant-free LNP- or IAJD-based therapeutics that induce antigen-specific regulatory T cell responses, selective modification platforms for pathogenic effector cells, and targeted immunomodulation of regulatory T cells — all approaches never previously tested in humans. Working in close coordination with CECTA, CREATE integrates discovery, in vitro and animal studies, and early-phase clinical trials, with Phase I human testing targeted by Year 2 and a Penn GMP facility coming online within 12–18 months. Industry partnerships with BioNTech, Orbital Therapeutics, and Zipcode Bio are already underway.

Impact & Innovation

Three new categories of mRNA therapy for autoimmune disease.

 

CREATE is pioneering adjuvant-free LNP therapeutics, pathogenic effector cell modification, and regulatory T cell immunomodulation — three mRNA-based treatment categories never tested in humans — with Phase I trials targeted by Year 2 and a GMP facility coming online within 18 months.

  • Introduces three entirely novel mRNA-based therapeutic modalities for autoimmune disease, complementing CAR T approaches with non-cell therapy platforms that could fundamentally transform how autoimmune conditions are treated at the cellular level
  • Generates substantial IP opportunities through novel in vivo mRNA therapeutic platforms, with active industry discussions with BioNTech, Orbital Therapeutics, and Zipcode Bio, and a Penn GMP facility creating multiple pathways for licensing, spin-out, and commercialization
  • Advances the Consortium’s From Mechanistic Insight to Translation pillar by building an integrated bench-to-bedside mRNA therapeutic pipeline — from construct development through GMP manufacturing, regulatory framework establishment, and Phase I/II clinical trials — across multiple severe autoimmune diseases
Research Approach

A framework designed for discovery

CREATE combines mRNA construct design, GMP manufacturing infrastructure development, and coordinated preclinical-to-clinical translation to advance three novel categories of mRNA-LNP therapeutics for autoimmune disease. The work integrates discovery science, in vitro and animal studies, and early-phase clinical trial preparation in close coordination with CECTA.

Design and testing of non-inflammatory, targeted mRNA-LNP and IAJD-based constructs across three therapeutic categories — antigen-specific Treg induction, pathogenic effector cell modification, and regulatory T cell immunomodulation; GMP-condition manufacturing of lead constructs; in vitro and animal study validation; and establishment of regulatory and logistical frameworks for Phase I and II clinical trials.

In vitro functional datasets validating mRNA-LNP construct activity across therapeutic categories; animal model efficacy and safety datasets; immunoprofiling insights from CECTA clinical trial patients informing construct design; and GMP manufacturing development data from the Penn RNA Institute infrastructure.

Advancement of three novel mRNA-based autoimmune therapeutic categories from construct development through GMP manufacturing and Phase I human trials, targeting type 1 diabetes, lupus, multiple sclerosis, and other severe autoimmune conditions. With the Penn GMP facility operational within 12–18 months and established industry partnerships, CREATE is positioned to deliver the first-ever human trials of these mRNA autoimmune therapeutics.

Investigators & Institutions

Powering the science

Principal Investigators

Ali Naji, MD, PhD, Colton Consortium Member

Jonathan E. Rhoads Professor of Surgical Science II, Department of Surgery, Perelman School of Medicine, University of Pennsylvania

Drew Weissman, MD, PhD, Colton Consortium Member

Roberts Family Professor in Vaccine Research, Department of Medicine, Perelman School of Medicine, University of Pennsylvania

Peter Merkel, MD, MPH, Colton Consortium Member

Professor of Medicine and Epidemiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania

Colton Centers & Institutions

Colton Center for Autoimmunity at the University of Pennsylvania

Perelman School of Medicine

Research Outputs

From insight to impact