Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery

Nature Medicine
John A MiksztaNoel G Harvey

Abstract

Skin is an attractive target for delivery of genetic therapies and vaccines. However, new approaches are needed to access this tissue more effectively. Here, we describe a new delivery technology based on arrays of structurally precise, micron-scale silicon projections, which we term microenhancer arrays (MEAs). In a human clinical study, these devices effectively breached the skin barrier, allowing direct access to the epidermis with minimal associated discomfort and skin irritation. In a mouse model, MEA-based delivery enabled topical gene transfer resulting in reporter gene activity up to 2,800-fold above topical controls. MEA-based delivery enabled topical immunization with naked plasmid DNA, inducing stronger and less variable immune responses than via needle-based injections, and reduced the number of immunizations required for full seroconversion. Together, the results provide the first in vivo use of microfabricated devices to breach the skin barrier and deliver vaccines topically, suggesting significant clinical and practical advantages over existing technologies.

References

Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·E RazM A Yankauckas
Dec 1, 1995·Human Molecular Genetics·M Y Alexander, R J Akhurst
May 1, 1997·The Journal of Investigative Dermatology·B LuG Scott
Aug 21, 1997·Nature·D C TangD T Curiel
Mar 20, 1999·The Journal of Investigative Dermatology·W H YuR J Debs
Apr 1, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·S BabiukM Foldvari
Jun 15, 2000·Immunological Investigations·J P Schneck
Nov 10, 2001·Annual Review of Biomedical Engineering·D V McAllisterM R Prausnitz
Feb 1, 1998·Skin Research and Technology : Official Journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)·Y H Leow, H I Maibach

❮ Previous
Next ❯

Citations

Apr 19, 2005·Biomedical Microdevices·Melissa Ai Ling TeoShabbir Moochhala
Nov 26, 2005·Pharmaceutical Research·Wijaya MartantoMark R Prausnitz
May 23, 2006·Pharmaceutical Research·Jung-Hwan ParkMark R Prausnitz
Mar 27, 2007·Pharmaceutical Research·Harvinder S Gill, Mark R Prausnitz
Apr 1, 2010·Pharmaceutical Research·Haripriya Kalluri, Ajay K Banga
Jun 29, 2010·Pharmaceutical Research·Scott A BurtonKris Hansen
Feb 9, 2011·Pharmaceutical Research·Stan L BanksAudra L Stinchcomb
Mar 17, 2004·Advanced Drug Delivery Reviews·Mark R Prausnitz
Jul 17, 2013·Advanced Drug Delivery Reviews·Eric Nuxoll
Jun 12, 2003·Vaccine·Roopjeet KahlonJan P Dutz
Mar 31, 2010·Immunology and Cell Biology·Patrizia StoitznerChristoph H Tripp
Jul 20, 2010·Nature Medicine·Sean P SullivanMark R Prausnitz
Apr 7, 2005·Nature Medicine·Stanley A Plotkin
Oct 22, 2005·Nature Reviews. Immunology·Samir Mitragotri
Feb 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Daniel P WermelingAudra L Stinchcomb
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Qiyun ZhuRichard W Compans
Oct 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alexander K AndrianovGeorge Mutwiri
Mar 2, 2005·Diabetes Technology & Therapeutics·Ping M WangMark R Prausnitz
Jan 25, 2005·The Pediatric Infectious Disease Journal·Stanley A Plotkin
Aug 22, 2008·The Clinical Journal of Pain·Harvinder S GillMark R Prausnitz
Oct 13, 2006·Infection and Immunity·John A MiksztaRobert G Ulrich
Aug 3, 2010·AAPS PharmSciTech·Yeu-Chun KimMark R Prausnitz
Jan 7, 2014·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Hidemasa KatsumiAkira Yamamoto
Mar 11, 2009·PloS One·Dimitrios G KoutsonanosIoanna Skountzou
Aug 28, 2007·International Journal of Nanomedicine·Tania Betancourt, Lisa Brannon-Peppas
Dec 24, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ana CoutoAna M Pessoa
Nov 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Devin V McAllisterMark R Prausnitz
Jan 29, 2013·Nature Materials·Peter C DeMuthDarrell J Irvine
Jul 30, 2011·Drug Delivery and Translational Research·Yeu-Chun Kim, Mark R Prausnitz
Feb 18, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Joanne McCaffreyHelen O McCarthy
Nov 13, 2015·Expert Opinion on Drug Delivery·N Sanoj RejinoldYeu-Chun Kim
Oct 11, 2011·Drug Development and Industrial Pharmacy·Chandra Sekhar KolliR Jayachandra Babu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Polyendocrine Syndromes

This feed focuses on a rare genetic condition called Autoimmune Polyendocrine Syndromes, which are characterized by autoantibodies against multiple endocrine organs. This can lead to Type I Diabetes.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
D V McAllisterMark R Prausnitz
Advanced Drug Delivery Reviews
Mark R Prausnitz
Pharmaceutical Research
Wijaya MartantoMark R Prausnitz
© 2022 Meta ULC. All rights reserved