Journal article
Efficient expression of stabilized mRNA PEG-peptide polyplexes in liver
Gene therapy, Vol.22(12), pp.993-999
12/2015
DOI: 10.1038/gt.2015.68
PMCID: PMC4670273
PMID: 26125604
Abstract
The expression efficiency in liver following hydrodynamic delivery of in vitro transcribed mRNA was improved 2000-fold using a codon-optimized mRNA luciferase construct with flanking 3' and 5' human β-globin untranslated regions (UTR mRNA) over an unoptimized mRNA without β-globin UTRs. Nanoparticle UTR mRNA polyplexes were formed using a novel polyacridine polyethylene glycol (PEG) peptide, resulting in an additional 15-fold increase in expression efficiency in the liver. The combined increase in expression for UTR mRNA PEG-peptide polyplexes was 3500-fold over mRNA lacking UTRs and PEG-peptide. The expression efficiency of UTR mRNA polyplex was 10-fold greater than the expression from an equivalent 1 μg dose of pGL3. Maximal expression was maintained from 4 to 24 h. Serum incubation established the unique ability of the polyacridine PEG-peptide to protect UTR mRNA polyplexes from RNase metabolism by binding to double-stranded regions. UTR mRNA PEG-peptide polyplexes are efficient nonviral vectors that circumvent the need for a nuclear uptake, representing an advancement toward the development of a targeted gene delivery system to transfect liver hepatocytes.
Details
- Title: Subtitle
- Efficient expression of stabilized mRNA PEG-peptide polyplexes in liver
- Creators
- S T Crowley - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USAJ A Poliskey - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USAN J Baumhover - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USAK G Rice - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.22(12), pp.993-999
- DOI
- 10.1038/gt.2015.68
- PMID
- 26125604
- PMCID
- PMC4670273
- NLM abbreviation
- Gene Ther
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Publisher
- England
- Grant note
- R01 GM097093 / NIGMS NIH HHS GM097093 / NIGMS NIH HHS T32 GM008365 / NIGMS NIH HHS
- Language
- English
- Date published
- 12/2015
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065311102771
Metrics
16 Record Views