Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ

Vaccines
Yen CuAndrew J Geall

Abstract

Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA.

References

Mar 23, 1990·Science·J A WolffP L Felgner
Jul 1, 1993·European Journal of Immunology·F MartinonP Meulien
Jan 8, 1999·Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie·L M MirD Scherman
Apr 26, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G WideraJ B Ulmer
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M DupuisD M McDonald
Sep 5, 2002·Reviews in Medical Virology·Jonathan O RaynerKurt I Kamrud
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Regina M KoflerChristian W Mandl
Jul 23, 2004·Expert Opinion on Biological Therapy·Steve Pascolo
Sep 21, 2004·Cellular and Molecular Life Sciences : CMLS·J-P CarralotS Pascolo
Oct 30, 2004·The Journal of Gene Medicine·Eirik GrønevikIacob Mathiesen
Dec 8, 2007·Current Opinion in Biotechnology·Marjorie Robert-Guroff
Dec 12, 2007·Handbook of Experimental Pharmacology·Veit HornungGunther Hartmann
Nov 13, 2008·Expert Reviews in Molecular Medicine·Gregory J AtkinsBrian J Sheahan
Nov 26, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Adil I DaudRichard Heller
Sep 1, 2009·Molecular Medicine Reports·John M PiggottGregory J Atkins
May 3, 2011·Current Opinion in Immunology·Niranjan Y Sardesai, David B Weiner
Sep 3, 2011·Immunological Reviews·Glen N Barber
Jan 13, 2012·PloS One·Daniel X JohanssonPeter Liljeström
Jan 20, 2012·Journal of Virology·Søren Jensen, Allan Randrup Thomsen
Mar 24, 2012·Current Opinion in Virology·Natalie A HutnickDavid B Weiner
Aug 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Andrew J GeallChristian W Mandl
Oct 12, 2012·Science Translational Medicine·Mark L BagarazziNiranjan Y Sardesai
Jan 25, 2013·Molecular Therapy. Nucleic Acids·Kate E BroderickNiranjan Y Sardesai
Jun 6, 2013·Seminars in Immunology·Andrew J GeallJeffrey B Ulmer

❮ Previous
Next ❯

Citations

Oct 2, 2014·Expert Review of Vaccines·Karl Ljungberg, Peter Liljeström
Mar 29, 2014·Expert Opinion on Drug Delivery·Raquel P DeeringAndrew J Geall
Jun 20, 2015·Human Vaccines & Immunotherapeutics·Fatemeh Nazly PirmoradiEugene M Chow
Nov 20, 2016·Annual Review of Animal Biosciences·Mia C Hikke, Gorben P Pijlman
Mar 1, 2017·Nature Biotechnology·Steven F Dowdy
Feb 6, 2020·Pharmaceutics·Abishek WadhwaAneesh Thakur
Jul 16, 2019·Molecular Therapy. Nucleic Acids·Hanne HuysmansNiek N Sanders
Sep 9, 2020·Current Opinion in Virology·María Cristina Ballesteros-BrionesCristian Smerdou
Feb 11, 2021·Vaccines·Zekun MuDerek W Cain
Oct 24, 2020·Gene Therapy·Kristie BloomPatrick Arbuthnot
Jan 11, 2021·Advanced Drug Delivery Reviews·Deborah PushparajahRoderick A Slavcev
Aug 2, 2021·Molecular Aspects of Medicine·Manish PandeyGeetanjali Chawla

❮ Previous
Next ❯

Datasets Mentioned

BETA
U89937
KC896842.1

Methods Mentioned

BETA
ELISA
flow cytometry
restriction digest
fluorescence imaging
Assay

Software Mentioned

FlowJo
GraphPad Prism
GraphPad

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Expert Opinion on Drug Delivery
Raquel P DeeringAndrew J Geall
Vaccine
Jeffrey B UlmerChristian W Mandl
Molecular Therapy : the Journal of the American Society of Gene Therapy
Luis A BritoAndrew J Geall
Proceedings of the National Academy of Sciences of the United States of America
Andrew J GeallChristian W Mandl
© 2021 Meta ULC. All rights reserved