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Scientific reports2021; 11(1); 371; doi: 10.1038/s41598-020-79855-1

Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent.

Abstract: Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. We were able to safely and effectively transfect the bronchial epithelium of foals using naked mRNA (i.e., mRNA formulated in a sodium citrate buffer without a delivery vehicle). Endoscopic examination of the bronchial tree and histology of mucosal biopsies indicated no gross or microscopic adverse effects of the transfection. Our data suggest that mRNA administered by an atomization device eliminates the need for chemical transfection agents, which can reduce the cost and the safety risks of delivering mRNA to the respiratory tract of animals and humans.
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Publication Date: 2021-01-11 PubMed ID: 33432084PubMed Central: PMC7801524DOI: 10.1038/s41598-020-79855-1Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the potential of using in vitro transcribed mRNA to make vaccines and therapeutics more effectively and safely by aerosolizing the mRNA into micron-sized droplets, eliminating the need for transfection agents in the process. This technique was successfully tested on the respiratory tract epithelium of horses.

Introduction to the Research

  • The research focuses on exploring the potential of using in vitro transcribed mRNA in veterinary and human medicine. mRNA is used to produce vaccines and therapeutics. The study sought to find a safe and effective way of delivering this mRNA to the cells.
  • Traditionally, transfection agents are used for this purpose. These are substances that help protect the mRNA and enhance its ability to enter the cells (transfection). However, these transfection agents come with their own drawbacks – they add expense and they raise concerns regarding quality control and safety.

The Study and its Findings

  • The researchers did away with complex mRNA delivery systems by aerosolizing the mRNA into micron-sized droplets to transfect epithelial cells.
  • They then tested this method on an in vivo model by using horses, specifically focusing on the bronchial epithelium in foals. They found that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. This shows that the mRNA can function without the need for these agents.
  • Such mRNA is termed ‘naked’ mRNA since it is formulated in a sodium citrate buffer without a delivery vehicle or transfection agent.
  • The researchers found no adverse effects from the mRNA transfection, both on the surface examination of the bronchial tree and upon histological examination of mucosal biopsies. This demonstrates that their method can be considered safe.

Implications of the Research

  • By eliminating the need for chemical transfection agents, this new method of administering mRNA by an atomization device can reduce the cost and safety risks associated with using mRNA in the respiratory tract of animals and humans.
  • This method will potentially make the creation and delivery of mRNA based vaccines and therapeutics safer, simpler, and more cost-effective.

Cite This Article

APA
Legere RM, Cohen ND, Poveda C, Bray JM, Barhoumi R, Szule JA, de la Concha-Bermejillo A, Bordin AI, Pollet J. (2021). Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent. Sci Rep, 11(1), 371. https://doi.org/10.1038/s41598-020-79855-1

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 371
PII: 371

Researcher Affiliations

Legere, Rebecca M
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
Cohen, Noah D
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA. ncohen@cvm.tamu.edu.
Poveda, Cristina
  • Department of Pediatrics, National School of Tropical Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Bray, Jocelyne M
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
Barhoumi, Rola
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
Szule, Joseph A
  • Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
de la Concha-Bermejillo, Andrés
  • Texas A&M Veterinary Medical Diagnostic Laboratory, Texas A&M University, College Station, TX, USA.
Bordin, Angela I
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
Pollet, Jeroen
  • Department of Pediatrics, National School of Tropical Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Jeroen.pollet@bcm.edu.
  • Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, 1102 Bates Street, Houston, TX, USA. Jeroen.pollet@bcm.edu.

MeSH Terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Drug Carriers / administration & dosage
  • Drug Carriers / adverse effects
  • Drug Carriers / pharmacokinetics
  • Drug Delivery Systems / adverse effects
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / veterinary
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Horses
  • Lung / drug effects
  • Lung / metabolism
  • Nasal Sprays
  • Nebulizers and Vaporizers / veterinary
  • Polyethyleneimine / administration & dosage
  • Polyethyleneimine / chemistry
  • RNA, Messenger / administration & dosage
  • RNA, Messenger / adverse effects
  • RNA, Messenger / pharmacokinetics
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Transcription, Genetic
  • Transfection / methods
  • Transfection / veterinary
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / pharmacokinetics

Conflict of Interest Statement

The authors declare no competing interests.

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Citations

This article has been cited 9 times.
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