Abstract
833. Metabolically Stabilized Non-Viral Gene Delivery Systems
Molecular therapy, Vol.9(S1), pp.S316-S316
05/01/2004
DOI: 10.1016/j.ymthe.2004.06.734
Abstract
Peptide-based gene delivery systems are composed of synthetic (20 amino acid) peptides derivatized with a targeting oligosaccharide or a polyethylene glycol chain (PEG) 1,2 . Ad-mixtures of the glycopeptide and PEG-peptide conjugates were used to form DNA condensates that were stabilized by glutaraldehyde cross-linking through formation of a di-Schiffs base. The degree of metabolic stability is directly related to the degree of glutaraldehyde crosslinking, with metabolic half-lives in mouse liver ranging from 2 hours to 3 days 3 .In the present study we demonstrate that the metabolic half-life of cross-linked peptide DNA condensates in liver can be significantly extended following reduction of Schiff-bases. Zeta potential analysis revealed that electro positive peptide-DNA condensates became electro neutral upon reaction with glutaraldehyde when forming Schiff-bases. Reduction with borane dimethylamine complex led to the formation of electro positive particles due to the formation of secondary amines.Reductively stabilized cross-linked DNA condensates demonstrated a liver half life of 5 days. Comparison of identical formulations composed of either L or D-amino acids failed to further increase in the metabolic half-life of either reduced or non-reduced crosslinked peptide-DNA condensates.The results suggest that reversal of di-Schiffs bases on cross-linked DNA condensates contribute to the metabolic half-life of peptide-DNA condensates in vivo. However, the route of metabolism for reduced cross-linked D-peptide DNA condensates remains unclear since these formulations should neither undergo cross-linking reversal nor proteolytic cleavage to release DNA.
Details
- Title: Subtitle
- 833. Metabolically Stabilized Non-Viral Gene Delivery Systems
- Creators
- Dijie LiuMolly MartinChangpo ChenKevin Rice
- Resource Type
- Abstract
- Publication Details
- Molecular therapy, Vol.9(S1), pp.S316-S316
- DOI
- 10.1016/j.ymthe.2004.06.734
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Publisher
- Elsevier Limited
- Language
- English
- Date published
- 05/01/2004
- Academic Unit
- Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Pharmacy Practice and Science; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984366312402771
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