Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2008.01.031
Title: An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection
Authors: Lo, S.L.
Wang, S. 
Keywords: Gene transfer
Nanoparticle
Peptide
Self assembly
Issue Date: May-2008
Citation: Lo, S.L., Wang, S. (2008-05). An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection. Biomaterials 29 (15) : 2408-2414. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2008.01.031
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. © 2008 Elsevier Ltd. All rights reserved.
Source Title: Biomaterials
URI: http://scholarbank.nus.edu.sg/handle/10635/100060
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2008.01.031
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

191
checked on May 20, 2018

WEB OF SCIENCETM
Citations

166
checked on Apr 23, 2018

Page view(s)

34
checked on May 18, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.