Derivation of a triple mosaic adenovirus for cancer gene therapy

Yizhe Tang, Hongju Wu, Hideyo Ugai, Qiana L. Matthews, David T. Curiel

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improvements are needed in order for Ad vectors to be effective cancer therapeutics, which include, but are not limited to, improvement of cellular uptake, enhanced cancer cell killing activity, and the capability of vector visualization and tracking once injected into the patients. To this end, we attempted to develop an Ad as a multifunctional platform incorporating targeting, imaging, and therapeutic motifs. In this study, we explored the utility of this proposed platform by generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our study herein demonstrates the generation of the triple mosaic Ad vector with pK, HSV-1 TK, and mRFP1 at the carboxyl termini of Ad minor capsid protein IX (pIX). In addition, the functionalities of pK, HSV-1 TK, and mRFP1 proteins on the Ad vector were retained as confirmed by corresponding functional assays, indicating the potential multifunctional application of this new Ad vector for cancer gene therapy. The validation of the triple mosaic Ad vectors also argues for the ability of pIX modification as a base for the development of multifunctional Ad vectors.

Original languageEnglish (US)
Article numbere8526
JournalPLoS One
Volume4
Issue number12
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Gene therapy
gene therapy
Neoplasm Genes
Adenoviridae
Genetic Therapy
thymidine kinase
Human herpesvirus 1
neoplasms
Thymidine Kinase
Human Herpesvirus 1
therapeutics
Neoplasms
Viruses
medicine
image analysis
Therapeutics
coat proteins
Medicine
Capsid Proteins
lysine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tang, Y., Wu, H., Ugai, H., Matthews, Q. L., & Curiel, D. T. (2009). Derivation of a triple mosaic adenovirus for cancer gene therapy. PLoS One, 4(12), [e8526]. https://doi.org/10.1371/journal.pone.0008526

Derivation of a triple mosaic adenovirus for cancer gene therapy. / Tang, Yizhe; Wu, Hongju; Ugai, Hideyo; Matthews, Qiana L.; Curiel, David T.

In: PLoS One, Vol. 4, No. 12, e8526, 2009.

Research output: Contribution to journalArticle

Tang, Y, Wu, H, Ugai, H, Matthews, QL & Curiel, DT 2009, 'Derivation of a triple mosaic adenovirus for cancer gene therapy', PLoS One, vol. 4, no. 12, e8526. https://doi.org/10.1371/journal.pone.0008526
Tang, Yizhe ; Wu, Hongju ; Ugai, Hideyo ; Matthews, Qiana L. ; Curiel, David T. / Derivation of a triple mosaic adenovirus for cancer gene therapy. In: PLoS One. 2009 ; Vol. 4, No. 12.
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