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PENN

HOME > 연구 공간 > mRNA Therapeutics Joint Research > PENN
  • Mitchell Lab

    School of Engineering and Applied Science
    University of Pennsylvania
    (Principal Investigator: Michael J. Mitchell, Ph.D.)

  • Mailing Address

    240 Skirkanich Hall 210 South 33rd Street Philadelphia, PA 19104-6321, United States of America

  • Tel

    +1-215-898-0882

  • Email

    mjmitch@seas.upenn.edu

  • URL

    https://mitchell-lab.seas.upenn.edu/

Global Collaboration on the Creation of Novel saRNA Vectors for Nasal Vaccine

Context & Rationale

With the onset of COVID-19, there has been a global race to develop effective mRNA vaccine platforms. These vaccines offer benefits like better delivery efficacy, safety, and cost-effectiveness. However, current vaccines, mainly designed for intramuscular use, show limited efficiency in preventing respiratory transmission. To address this, intranasal vaccination emerges as a potential solution. Yet, challenges like limited intranasal mRNA transfection efficiency and inadequate immune responses persist. This stems from factors such as mucus barriers and the intranasal administration's constraints. As such, there's a need to develop innovative lipid compositions and mRNA designs for intranasal use.

Innovative Approach

The proposal involves creating advanced mRNA lipid nanoparticles with features like self-amplifying mRNA, ionizable lipids, and targeting PEG-lipids. Self-amplifying mRNA can achieve higher immunogen expression with much less mRNA compared to conventional vaccines like Pfizer and Moderna. The incorporation of ionizable lipids might enhance transfection efficiency, and using targeting PEG-lipids could boost retention in the deep lung, improving intranasal mRNA delivery. Together, these advancements could overcome existing intranasal mRNA delivery challenges and pave the way for future vaccine development.

Goals & Collaboration

The collaborative endeavor between UPENN and KRIBB aims for significant breakthroughs in the field by 2024.

Specific Aims

  • 1. Utilizing Existing Lipids : The teams plan to utilize UPENN’s current ionizable lipids to formulate lipid nanoparticles (LNP) for efficient mRNA vaccine delivery. By encapsulating self-amplifying mRNAs in these lipids and assessing their efficacy via bioluminescence imaging, the best LNP formulation for intranasal delivery can be identified.
  • 2. Developing Novel Lipids : The teams will also endeavor to design and screen new ionizable lipids optimized for intranasal delivery. The goal is to enhance the efficacy of self-amplifying mRNA, aiming for a vaccine dosage under 1 microgram.

Risk Assessment

The intranasal delivery route does have inherent challenges such as mucus barriers and limited volumes. It is imperative to evaluate the mRNA lipid nanoparticles' efficacy and safety both in vitro and in vivo. Initial evaluations will focus on transfection efficiency and toxicity, while in vivo assessments will look at deep lung accumulation and the immune response generated.

Significance

The proposed work could be groundbreaking in the realm of intranasal vaccine development. The meticulous and innovative approach towards lipid nanoparticle design holds the promise of a significant leap in the fight against respiratory transmitted diseases like COVID-19.