Intratumor RNA interference of cell cycle genes slows down tumor progression

S. Dharmapuri, D. Peruzzi, E. Marra, F. Palombo, A. J. Bett, S. R. Bartz, M. Yong, G. Ciliberto, N. La Monica, C. A. Buser, C. Toniatti, L. Aurisicchio

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Small interfering RNAs (siRNAs) are emerging as promising therapeutic tools. However, the widespread clinical application of such molecules as modulators of gene expression is still dependent on several aspects that limit their bioavailability. One of the most promising strategies to overcome the barriers faced by gene silencing molecules involves the use of lipid-based nanoparticles (LNPs) and viral vectors, such as adenoviruses (Ads). The primary obstacle for translating gene silencing technology from an effective research tool into a feasible therapeutic strategy remains its efficient delivery to the targeted cell type in vivo. In this study, we tested the capability of LNPs and Ad to transduce and treat locally tumors in vivo. Efficient knockdown of a surrogate reporter (luciferase) and therapeutic target genes such as the kinesin spindle protein (KIF11) and polo-like kinase 1 were observed. Most importantly, this activity led to a cell cycle block as a consequence and slowed down tumor progression in tumor-bearing animals. Our data indicate that it is possible to achieve tumor transduction with si/short hairpin RNAs and further improve the delivery strategy that likely in the future will lead to the ideal non-viral particle for targeted cancer gene silencing.

Original languageEnglish
Pages (from-to)727-733
Number of pages7
JournalGene Therapy
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 2011

Fingerprint

cdc Genes
RNA Interference
Gene Silencing
Nanoparticles
Small Interfering RNA
Neoplasms
Lipids
Kinesin
Neoplasm Genes
Luciferases
Adenoviridae
Biological Availability
Cell Cycle
Therapeutics
Technology
Gene Expression
Research
Genes
Proteins

Keywords

  • KSP
  • liponanoparticle
  • PLK1
  • siRNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Dharmapuri, S., Peruzzi, D., Marra, E., Palombo, F., Bett, A. J., Bartz, S. R., ... Aurisicchio, L. (2011). Intratumor RNA interference of cell cycle genes slows down tumor progression. Gene Therapy, 18(7), 727-733. https://doi.org/10.1038/gt.2011.27

Intratumor RNA interference of cell cycle genes slows down tumor progression. / Dharmapuri, S.; Peruzzi, D.; Marra, E.; Palombo, F.; Bett, A. J.; Bartz, S. R.; Yong, M.; Ciliberto, G.; La Monica, N.; Buser, C. A.; Toniatti, C.; Aurisicchio, L.

In: Gene Therapy, Vol. 18, No. 7, 07.2011, p. 727-733.

Research output: Contribution to journalArticle

Dharmapuri, S, Peruzzi, D, Marra, E, Palombo, F, Bett, AJ, Bartz, SR, Yong, M, Ciliberto, G, La Monica, N, Buser, CA, Toniatti, C & Aurisicchio, L 2011, 'Intratumor RNA interference of cell cycle genes slows down tumor progression', Gene Therapy, vol. 18, no. 7, pp. 727-733. https://doi.org/10.1038/gt.2011.27
Dharmapuri S, Peruzzi D, Marra E, Palombo F, Bett AJ, Bartz SR et al. Intratumor RNA interference of cell cycle genes slows down tumor progression. Gene Therapy. 2011 Jul;18(7):727-733. https://doi.org/10.1038/gt.2011.27
Dharmapuri, S. ; Peruzzi, D. ; Marra, E. ; Palombo, F. ; Bett, A. J. ; Bartz, S. R. ; Yong, M. ; Ciliberto, G. ; La Monica, N. ; Buser, C. A. ; Toniatti, C. ; Aurisicchio, L. / Intratumor RNA interference of cell cycle genes slows down tumor progression. In: Gene Therapy. 2011 ; Vol. 18, No. 7. pp. 727-733.
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