Development and application of adenoviral vectors for gene therapy of cancer

Zhang, Weiwei

doi:10.1038/sj.cgt.7700024

Cited by 164 publications

(85 citation statements)

References 125 publications

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“…1,2 However, a selective delivery of a therapeutic gene to target cells by adenovirus vectors is precluded by the widespread distribution of the primary cellular receptors for adenoviruses. 3,4 Therefore, strategies are being developed to redirect the tropism of the adenovirus vector to permit efficient target gene delivery to specific cell types.…”

Section: Introductionmentioning

confidence: 99%

Direct selection of targeted adenovirus vectors by random peptide display on the fiber knob

Miura¹,

Yoshida²,

Nishimoto³

et al. 2007

Gene Ther

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Targeting of gene transfer at the level of cell entry is one of the most attractive challenges in vector development. However, attempts to redirect adenovirus vectors to alternative receptors by engineering the capsid-coding region have shown limited success because proper targeting ligand-receptor systems on the cells of interest are generally unknown. Systematic approaches to generate adenovirus vectors targeting any given cell type need to be developed to achieve this goal. Here, we constructed an adenovirus library that was generated by a Cre-lox-mediated in vitro recombination between an adenoviral fiber-modified plasmid library and genomic DNA to display random peptides on a fiber knob. As proof of concept, we screened the adenovirus display library on a glioma cell line and observed selection of several particular peptide sequences. The targeted vector carrying the most frequently isolated peptide significantly enhanced gene transduction in the glioma cell line but not in many other cell lines. Because the insertion of a pre-selected peptide into a fiber knob often fails to generate an adenovirus vector, the selection of targeting peptides is highly useful in the context of the adenoviral capsid. This vector-screening system can facilitate the development of a targeted adenovirus vector for a variety of applications in medicine.

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Section: Introductionmentioning

confidence: 99%

Direct selection of targeted adenovirus vectors by random peptide display on the fiber knob

Miura¹,

Yoshida²,

Nishimoto³

et al. 2007

Gene Ther

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“…33 Ads are nonenveloped double-stranded DNA viruses whose capsid is mainly composed of pentons (penton base and fiber monomers) and hexons. The viral cycle begins with the attachment of the fiber to a cellular receptor, which in the case of the widely used Adenovirus serotype 5 (Ad5) is the Coxsackievirus and Adenovirus receptor (CAR) followed by the interaction of the penton base with proteins belonging to the integrin family.…”

Section: Ad As a Vector For Gene Deliverymentioning

confidence: 99%

Adenovirus as vehicle for anticancer genetic immunotherapy

et al. 2005

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Adenoviruses (Ads) are in the forefront of genetic immunization methods being developed against cancer. Their ability to elicit an effective immune response against tumorassociated antigens has been demonstrated in many model systems. Several clinical trials, which use Ad as vehicle for immunization, are already in progress. Preclinical studies have also demonstrated the efficacy of combining Ad-mediated immunization with adjuvants such as chemotherapeutic agents and cytokines. Issues related to sero-prevalence and safety of Ads, however, continue to pose a challenge and need to be addressed. Gene Therapy (2005) 12, S84-S91.

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“…1,2 Viral vectors function by replicating to toxic levels within infected cells or by delivering a 'suicide gene' encoding enzymes to locally modify systemically administered non-toxic drugs into their toxic metabolites. 3,4 Additionally, therapeutic genes inserted into the vector may be infected into specific host tissues to produce a biological effect.…”

Section: Introductionmentioning

confidence: 99%