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Hybrid nanomaterial complexes for advanced phage-guided gene delivery
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Document Title
Hybrid nanomaterial complexes for advanced phage-guided gene delivery
Author
Yata T., Lee K.-Y., Dharakul T., Songsivilai S., Bismarck A., Mintz P.J., Hajitou A.
Name from Authors Collection
Affiliations
Department of Medicine, Phage Therapy Group, Imperial College London, London, United Kingdom; Department of Chemical Engineering, Polymers and Composites Engineering (PaCE) Group, Imperial College London, London, United Kingdom; National Nanotechnology Center, National Science and Technology Development Agency, Khlong Luang Pathumthani, Thailand; Department of Surgery and Cancer, Imperial College London, London, United Kingdom; Department of Medicine, Imperial College London, Hammersmith Hospital Campus, 160 Du Cane Road, London W12 0NN, United Kingdom
Type
Article
Source Title
Molecular Therapy - Nucleic Acids
ISSN
21622531
Year
2014
Volume
3
Page
e185-
Open Access
Gold, Green
Publisher
Nature Publishing Group
DOI
10.1038/mtna.2014.37
Abstract
Developing nanomaterials that are effective, safe, and selective for gene transfer applications is challenging. Bacteriophages (phage), viruses that infect bacteria only, have shown promise for targeted gene transfer applications. Unfortunately, limited progress has been achieved in improving their potential to overcome mammalian cellular barriers. We hypothesized that chemical modification of the bacteriophage capsid could be applied to improve targeted gene delivery by phage vectors into mammalian cells. Here, we introduce a novel hybrid system consisting of two classes of nanomaterial systems, cationic polymers and M13 bacteriophage virus particles genetically engineered to display a tumor-targeting ligand and carry a transgene cassette. We demonstrate that the phage complex with cationic polymers generates positively charged phage and large aggregates that show enhanced cell surface attachment, buffering capacity, and improved transgene expression while retaining cell type specificity. Moreover, phage/polymer complexes carrying a therapeutic gene achieve greater cancer cell killing than phage alone. This new class of hybrid nanomaterial platform can advance targeted gene delivery applications by bacteriophage. © 2014 The American Society of Gene & Cell Therapy All rights reserved.
Keyword
Bacteriophage | Biomaterials | cancer | Cationic Polymers | Targeted Gene Transfer | Viral Particles
Funding Sponsor
Medical Research Council
License
CC BY or CC BY-NC-ND
Rights
Elsevier B.V.
Publication Source
Scopus