Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin®) conjugated polyethylenimine

Chiu, Shih Jiuan; Ueno, Naoto T.; Lee, Robert J.

doi:10.1016/j.jconrel.2004.03.019

Cited by 135 publications

(83 citation statements)

References 45 publications

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“…The pDNA/PEI complex, however, binds non-specifically to negatively charged proteoglycans on cell membranes and it is difficult to use the cationic pDNA/PEI complex as the targeted gene delivery system (Lemkine and Demeneix, 2001;Demeneix and Behr, 2005). For cell-specific gene delivery, cell type-specific surface molecules and their antibodies would be useful, and a number of cell-specific gene delivery vectors have been developed (Germershaus, et al, 2006;Chiu, et al, 2004;Liu, et al, 2007). For cancer gene therapy, tumor suppressor genes such as p53 gene and suicide genes such as herpes simplex virus thymidine kinase gene were well studied; and those genes reported to suppress tumor growth by tumor specific gene delivery vector such as transferrin-modified cationic liposome (Nakase, et al, 2005;Neves, 2006).…”

Section: Introductionmentioning

confidence: 99%

Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer

Kurosaki

Higuchi

Kawakami

et al. 2012

Gene

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We have developed a novel vector constructed with pDNA, polyethylenimine (PEI), and mucin 1 (MUC1) aptamer for tumor-targeted gene delivery. The MUC1 aptamer and non-specific aptamer were employed to coat the pDNA/PEI complexes electrostatically and stable nanoparticles were formed. The addition of a non-specific aptamer to the pDNA/PEI complex decreased gene expression in the human lung cancer cell line, A549 cells expressing MUC1 regularly. At the same time, the pDNA/PEI/MUC1 aptamer complex showed higher gene expression than pDNA/PEI/non-specific aptamer complex. Furthermore, the pDNA/PEI/MUC1 aptamer complex showed markedly high gene expression in tumor-bearing mice; thus, pDNA/PEI/MUC1 aptamer complexes are useful as a tumor-targeted gene delivery system with high transfection efficiency.

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Section: Introductionmentioning

confidence: 99%

Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer

Kurosaki

Higuchi

Kawakami

et al. 2012

Gene

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“…This antibody-mediated uptake has been successfully used to deliver plasmid DNA and antisense oligonucleotides. [13][14][15][16][17] Recently, Song et al 18 demonstrated that siRNA targeted delivered to human immunodeficiency virus-infected cells and HER2 positive cells by this strategy executed gene silencing. However, whether this promising strategy for siRNA delivery is applicable to other diseases remains unknown.…”

mentioning

confidence: 99%

Targeted inhibition of HBV gene expression by single-chain antibody mediated small interfering RNA delivery

et al. 2007

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RNA interference is highly effective at inhibiting HBV gene expression and replication. However, before small interfering RNA (siRNA) can be used in the clinic, it is essential to develop a system to target their delivery. Antibody-mediated delivery is a novel approach for targeting siRNA to appropriate cells. In this report, we asked whether this siRNA delivery strategy would be effective against HBV. Of 5 candidates, a specific siRNA that effectively inhibited HBV gene expression and replication was determined. Two fusion proteins, s-tP and sC-tP, were constructed to contain a single chain of the human variable fragment, scFv, against hepatitis B surface antigen (HBsAg), a truncated protamine (tP), and in the case of sC-tP, a constant region of the chain (C). S-tP and sC-tP were developed to provide targeted delivery of the siRNA, siRNA expressing cassettes (SEC), and siRNA-producing plasmids. Fluorescein isothiocyanate-siRNA, fluorescein isothiocyanate-SEC, and plasmid DNA were specifically delivered into HBsAg-positive cells using the sC-tP fusion protein, and effectively inhibited HBV gene expression and replication. HBV gene expression was also inhibited by siRNA or siRNA-producing plasmids in HBV transgenic mice. Conclusion: Our results describe a potential method for the targeted delivery of siRNA or siRNAproducing plasmids against HBV, using anti-HBsAg fusion proteins. (HEPATOLOGY 2007;46: 84-94.) R ibonucleic acid interference is a naturally occurring mechanism for silencing homologous genes. 1,2 Synthetic and plasmid-based siRNA expression systems are both effective at suppressing HBV infection, in vitro and in vivo, [3][4][5][6][7][8][9] providing the basis for a new therapeutic strategy against HBV. However, the absence of a suitable delivery system presents a major obstacle against their clinical use. [10][11][12] Targeted delivery of small interfering RNA (siRNA) to relevant cell populations should increase the therapeutic index and minimize potential side effects and cellular toxicity.Antibody-mediated delivery is an effective method of targeting siRNA to particular cells. This involves fusing the nucleic acid-binding domain to a Fab fragment or scFv that recognizes a membrane receptor, resulting in a fusion protein that possesses cell recognition and nucleic acid-binding abilities. The fusion protein can then bind nucleic acids and deliver them into target cells through receptor-mediated endocytosis. This antibody-mediated uptake has been successfully used to deliver plasmid DNA and antisense oligonucleotides. [13][14][15][16][17] Song et al. 18 demonstrated that siRNA targeted delivered to human immunodeficiency virus-infected cells and HER2 positive cells by this strategy executed gene silencing. However, whether this promising strategy for siRNA delivery is applicable to other diseases remains unknown. 19 In this report, we provide evidence that antibody-mediated siRNA delivery is effectively targeted to HBV-infected cells.In a previous study, we have obtained 5 human antihepatitis B sur...

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“…As observed in viral vectors and lipoplexes, antibodies can be also conjugated with polyplexes to target genetic material to specific cell types. A successful overexpression of the human epidermal growth factor receptor-2 (HER2) by transfection with a polyplex conjugated with an anti-HER2 monoclonal antibody has been reported for a breast cancer cell line (Chiu et al, 2004). Another approach in adult MSCs used a modification of a PLL polymer with a palmitic acid substitution to target bone marrow stromal cells.…”

Section: Polyplexesmentioning

confidence: 99%

Gene Delivery Systems: Tailoring Vectors to Reach Specific Tissues

Alméciga-Díaz¹,

Cuaspa²,

Barrera³

2011

Non-Viral Gene Therapy

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Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin®) conjugated polyethylenimine

Cited by 135 publications

References 45 publications

Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer

Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer

Targeted inhibition of HBV gene expression by single-chain antibody mediated small interfering RNA delivery

Gene Delivery Systems: Tailoring Vectors to Reach Specific Tissues

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