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An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection

Paper ID Volume ID Publish Year Pages File Format Full-Text
10129 666 2008 7 PDF Available
Title
An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection
Abstract

Peptides as functional biomaterials offer the possibility of incorporating various biological activities required for different biomedical applications. Here, we take advantage of this property of peptide materials and design a DNA delivery vector equipped with multiple functions critical to efficient gene transfection. The Tat peptide, a cationic cell-penetrating peptide, is known to enhance the cellular uptake of a large variety of molecules such as drugs and proteins. However, the application of the Tat peptide in DNA delivery is limited by the inability to release DNA in endosomes and the instability of peptide/DNA complexes. We incorporate in the Tat sequence histidine and cysteine residues that are able to promote endosomal escape of DNA and protect DNA in the extracellular environment. We observe up to 7000-fold improvement in gene transfection efficiency by a modified Tat peptide covalently fused with 10 histidine residues (Tat-10H) over the original Tat peptide. After incorporating two cysteine residues into the Tat-10H design, the resulting bis(cysteinyl) histidine-rich peptide is more effective than the Tat-10H peptide, because interpeptide disulfide bonds form by air oxidation upon binding to DNA, leading to enhanced stability of peptide/DNA complexes. These findings demonstrate the feasibility of using multi-functional peptide materials to extend the applications of the Tat vector to efficient gene delivery.

Keywords
Gene transfer; Self assembly; Nanoparticle; Peptide
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An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 15, May 2008, Pages 2408–2414
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us