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Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019), Nature Communications
- Publication Year :
- 2019
- Publisher :
- Nature Portfolio, 2019.
-
Abstract
- Chemically modified mRNA is an efficient, biocompatible modality for therapeutic protein expression. We report a first-time-in-human study of this modality, aiming to evaluate safety and potential therapeutic effects. Men with type 2 diabetes mellitus (T2DM) received intradermal injections of modified mRNA encoding vascular endothelial growth factor A (VEGF-A) or buffered saline placebo (ethical obligations precluded use of a non-translatable mRNA control) at randomized sites on the forearm. The only causally treatment-related adverse events were mild injection-site reactions. Skin microdialysis revealed elevated VEGF-A protein levels at mRNA-treated sites versus placebo-treated sites from about 4–24 hours post-administration. Enhancements in basal skin blood flow at 4 hours and 7 days post-administration were detected using laser Doppler fluximetry and imaging. Intradermal VEGF-A mRNA was well tolerated and led to local functional VEGF-A protein expression and transient skin blood flow enhancement in men with T2DM. VEGF-A mRNA may have therapeutic potential for regenerative angiogenesis.<br />Chemically modified mRNA is a new approach for therapeutic protein expression that could be applied to angiogenesis. Here the authors show in a phase 1 clinical trial that a modified mRNA encoding VEGF-A is well tolerated in patients with type 2 diabetes.
- Subjects :
- 0301 basic medicine
Adult
Male
Vascular Endothelial Growth Factor A
Microdialysis
Injections, Intradermal
Angiogenesis
Science
General Physics and Astronomy
Neovascularization, Physiologic
02 engineering and technology
Type 2 diabetes
Pharmacology
General Biochemistry, Genetics and Molecular Biology
Article
Neovascularization
Placebos
03 medical and health sciences
Diabetes mellitus
Medicine
Humans
RNA, Messenger
lcsh:Science
Aged
Skin
Multidisciplinary
business.industry
Therapeutic effect
Type 2 Diabetes Mellitus
General Chemistry
Genetic Therapy
Middle Aged
021001 nanoscience & nanotechnology
medicine.disease
Vascular endothelial growth factor A
030104 developmental biology
Diabetes Mellitus, Type 2
Regional Blood Flow
lcsh:Q
medicine.symptom
0210 nano-technology
business
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....a749b65a9ebbba86a7b5d4121933c25b