Selective in vivo targeting of human liver tumors by optimized AAV3 vectors in a murine xenograft model

Chen Ling, Yuan Wang, Yuanhui Zhang, Anila Ejjigani, Zifei Yin, Yuan Lu, Lina Wang, Meng Wang, Jun Li, Zhongbo Hu, George V. Aslanidi, Li Zhong, Guangping Gao, Arun Srivastava, Changquan Ling

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Current challenges for recombinant adeno-associated virus (rAAV) vector-based cancer treatment include the low efficiency and the lack of specificity in vivo. rAAV serotype 3 (rAAV3) vectors have previously been shown to be ineffective in normal mouse tissues following systemic administration. In the present study, we report that rAAV3 vectors can efficiently target and transduce various human liver cancer cells in vivo. Elimination of specific surface-exposed serine and threonine residues on rAAV3 capsids results in further augmentation in the transduction efficiency of these vectors, without any change in the viral tropism and cellular receptor interactions. In addition, we have identified a potential chemotherapy drug, shikonin, as a multifunctional compound to inhibit liver tumor growth as well as to significantly enhance the efficacy of rAAV vector-based gene therapy in vivo. Furthermore, we also document that suppression of tumorigenesis in a human liver cancer xenograft model can be achieved through systemic administration of the optimized rAAV3 vectors carrying a therapeutic gene, and shikonin at a dose that does not lead to liver damage. Our research provides a novel means to achieve not only targeted delivery but also the potential for gene therapy of human liver cancer.

Original languageEnglish (US)
Pages (from-to)1023-1034
Number of pages12
JournalHuman gene therapy
Issue number12
StatePublished - Dec 1 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Mary Ann Liebert, Inc. 2014.


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