Transduction of adenovirus vectors modified with cell-penetrating peptides
| Autor: | Ratima Asavatanabodee, Yasuo Yoshioka, Shinsaku Nakagawa, Shinya Kida, Yohei Mukai, Mitsuko Maeda, Hiroyuki Mizuguchi, Naoki Okada, Koichi Kawasaki, Yusuke Eto |
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| Rok vydání: | 2009 |
| Předmět: |
endocrine system
Physiology animal diseases viruses Genetic enhancement Genetic Vectors Cell Biology Coxsackievirus Biochemistry Adenoviridae Cell Line Viral vector Cellular and Molecular Neuroscience chemistry.chemical_compound Transduction (genetics) Endocrinology Transduction Genetic medicine Humans Receptor virus diseases Heparan sulfate biology.organism_classification Molecular biology medicine.anatomical_structure chemistry Cell-penetrating peptide Peptides |
| Zdroj: | Peptides. 30:1548-1552 |
| ISSN: | 0196-9781 |
| DOI: | 10.1016/j.peptides.2009.05.017 |
| Popis: | Adenovirus vectors (Advs) are widely used for basic and clinical research because of their high transduction efficiency. However, they are poorly transduced into cells lacking the primary adenovirus receptor, the coxsackievirus and adenovirus receptor (CAR). Here, we generated Adv conjugated with cell-penetrating peptides (CPPs), such as Tat, octaarginine (R8) or proline-rich (Pro) peptides, and compared the transduction properties of these constructs. We constructed the Advs conjugated to the CPPs (CPP–Adv) by chemical conjugation. The CPP-conjugated Advs created with optimal modification ratios led to gene expression 1–2 log orders higher than unmodified Adv in CAR-negative cells. Tat-Adv and R8-Adv were taken up into the cells mainly through macropinocytosis, independently of the CAR. In addition, the cellular uptake of Tat-Adv was highly dependent on heparan sulfate on the cell surface, whereas that of R8-Adv was dependent on chondroitin sulfate B. These data suggest that the use of CPP-Advs with different cellular uptake pathways might create new methods for the delivery of Adv. The results obtained in this research encourage the use of CPP-peptide-modified Advs as an attractive tool for transducing cells and as useful platform vectors for gene therapy and basic research. |
| Databáze: | OpenAIRE |
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