• 四川大學(xué)華西醫(yī)院普通外科（成都610041）;

目的介紹目前關(guān)于肝癌基因治療靶向性研究的進(jìn)展。方法采用文獻(xiàn)回顧的方式對(duì)肝癌基因治療研究中采用的組織特異性載體系統(tǒng)以及細(xì)胞特異性基因表達(dá)調(diào)控系統(tǒng)等相關(guān)文獻(xiàn)進(jìn)行了綜述。結(jié)果合成的DNA轉(zhuǎn)運(yùn)系統(tǒng)和經(jīng)修飾的病毒載體體外轉(zhuǎn)染靶細(xì)胞后，可獲得顯著表達(dá)。目的基因細(xì)胞特異性表達(dá)主要是以甲胎蛋白或白蛋白基因的轉(zhuǎn)錄調(diào)控元件為基礎(chǔ)，體外實(shí)驗(yàn)顯示出較強(qiáng)的作用靶向性。其它基因治療策略也顯示了很好的應(yīng)用前景。結(jié)論尋找更具特異性和普遍性的肝癌抗原是解決基因治療靶向性的關(guān)鍵。根據(jù)疾病和患者的具體情況選擇合適的基因轉(zhuǎn)運(yùn)系統(tǒng)和調(diào)控元件是未來基因治療的方向。

引用本文： 趙永恒,綜述嚴(yán)律南,審校. 肝癌基因治療的靶向性研究進(jìn)展. 中國(guó)普外基礎(chǔ)與臨床雜志, 2002, 9(6): 445-447. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《中國(guó)普外基礎(chǔ)與臨床雜志》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

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2. Sharon N, Lis H. Lectins as cell recognition molecules [J]. Science, 1989; 246(4927)∶227.
3. Han J, Il Yeom Y. Specific gene transfer mediated by galactossylated polyLlysine into hepatoma cells [J]. Int J Pharm, 2000; 202(1-2)∶51.
4. Park JU, Ishihara T, Kano A, et al. Preparation of dendritic graft coplymer consisting of poly（llysine） and arabinogalactan as a hepatocyte specific DNA carrier [J]. Prep Biochem Biotechnol, 1999;29(4)∶353.
5. Junbo H, Li Q, Zaide W, et al. Receptormediated interlukin2 gene transfer into human hepatoma cells [J]. Int J Mol Med, 1999; 3(6)∶601.
6. Takahashi H, Ozturk M, Wilson B, et al. In vivo expression of two novel tumorassociated antigens and their use in immunolocalization of human hepatocellular carcinoma [J]. Hepatology, 1989; 9(4)∶625.
7. Wilson B, Qzuturk M, Takahashi H, et al. Cell surface changes associated with transformation of human hepatocytes to the malignant phenotype [J]. Proc Natl Acad Sci USA, 1988; 85(9)∶3140.
8. Mohr L, Schauer JI, Boutin RH, et al. Targeted gene transfer to hepatocellular carcinoma cells in vitro using a novel monoclonal antibodybased gene delivery system [J]. Hepatology, 1999; 29(1)∶82.
9. Moradpour D, Compagnon B, Wilson BE, et al. Specific targeting of human hepatocellular carcinoma cells by immunoliposomes in vitro [J]. Hepatology, 1995; 22(5)∶1527.
10. Cotten M, LangleRouault F, Kirlappos H, et al. Transferrinpolycationmediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels [J]. Proc Natl Acad Sci USA, 1990; 87(11)∶4033.
11. Curiel DT, Agarwal S, Wagner E, et al. Adenovirus enhancement of transferrinpolylysinemediated gne delivery [J]. Proc Natl Acad Sci USA, 1991; 88(19)∶8850.
12. Moradpour D, Schauer JI, Zurawski VR, et al. Efficient gene transfer into mammalian cells with cholesterylspermidine [J]. Biochem Biophys Res Commun, 1996; 221(1)∶82.
13. Plank C , Mechtler K, Szoka FC Jr, et al. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery [J]. Hum Gene Ther, 1996; 7(12)∶1437.
14. Zern MA, Kresina TF. Hepatic drug delivery and gene therapy [J]. Hepatology, 1997; 25(2)∶484.
15. Somia NV, Zoppe M, Verma IM. Generation of targeted retroviral vectors by using singlechain variable fragment: an approach to in vivo gene delivery [J]. Proc Natl Acad Sci USA,1995; 92(16)∶7570.
16. Yang Y, Nunes FA, Bernencsi K, et al. Cellular immunity to viral antigens limits E1deleted adenovirus for gene therapy [J]. Proc Natl Acad Sci USA, 1994; 91(10)∶4407.
17. Engelhardt JF, Ye X, Doranz B, et al.Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver [J]. Proc Natl Acad Sci USA, 1994; 91(13)∶6196.
18. Ruoslahti E. Alphafetoprotein in cancer and fetal development [J] Adv Cancer Res,1979; 29∶275.
19. Xu GW, Sun ZT, Forrester K, et al. Tissuespecific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by retroviralmediated transfer of the wildtype P53 gene [J]. Hepatology, 1996; 24(5)∶1264.
20. Ido A, Nakata K, Kato Y, et al. Gene therapy for hepatoma cells using a retrovirus vector carring herpes simplex virus thymidine kinase gene under the control of human alphafetoprotein gene promoter [J]. Cancer Res, 1995; 55(14)∶3105.
21. Kanai F, Shiratori Y, Yoshida Y, et al. Gene therapy for alphafetoproteinproducing human hepatoma cells by adenovirusmediated transfer of the herpes simplex virus thymidine kinase gene [J]. Hepatology, 1996; 23(6)∶1359.
22. Su H, Lu R, Chang JC, et al. Tissuespecific expression of herpes simplex virus thymidine kinase gene delivered by adenoassociated virus inhibits the growth of human hepatocellular carcinoma in athymic mice [J]. Proc Natl Acad Sci USA, 1997; 94(25)∶13891.
23. Ohguchi S, Nakatsukasa H, Higashi T, et al. Expression of αfetoprotein and albumin genes in human hepatocellular carcinomas: limitations in the application of the genes for targeting human hepatocellular carcinoma in gene therapy [J]. Hepatology, 1998; 27(2)∶599.
24. Vollmer CM Jr, Eilber FC, Butterfield LH, et al. Alphafetoproteinspecific genetic immunotherapy for hepatocellular carcinoma [J]. Cancer Res,1999; 59(13)∶3064.
25. Gordon EM, Liu PX, Chen ZH, et al. Inhibition of metastatic tumor growth in nude mice by portal vein infusions of matrixtargeted retroviral vectors bearing a cytocidal cyclin G1 construct [J]. Cancer Res, 2000; 60(13)∶3343.
  1. 1. Zhang G, Budker V, Wolff JA. High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA [J]. Hum Gen Ther, 1999; 10(10)∶1735.
  2. 2. Sharon N, Lis H. Lectins as cell recognition molecules [J]. Science, 1989; 246(4927)∶227.
  3. 3. Han J, Il Yeom Y. Specific gene transfer mediated by galactossylated polyLlysine into hepatoma cells [J]. Int J Pharm, 2000; 202(1-2)∶51.
  4. 4. Park JU, Ishihara T, Kano A, et al. Preparation of dendritic graft coplymer consisting of poly（llysine） and arabinogalactan as a hepatocyte specific DNA carrier [J]. Prep Biochem Biotechnol, 1999;29(4)∶353.
  5. 5. Junbo H, Li Q, Zaide W, et al. Receptormediated interlukin2 gene transfer into human hepatoma cells [J]. Int J Mol Med, 1999; 3(6)∶601.
  6. 6. Takahashi H, Ozturk M, Wilson B, et al. In vivo expression of two novel tumorassociated antigens and their use in immunolocalization of human hepatocellular carcinoma [J]. Hepatology, 1989; 9(4)∶625.
  7. 7. Wilson B, Qzuturk M, Takahashi H, et al. Cell surface changes associated with transformation of human hepatocytes to the malignant phenotype [J]. Proc Natl Acad Sci USA, 1988; 85(9)∶3140.
  8. 8. Mohr L, Schauer JI, Boutin RH, et al. Targeted gene transfer to hepatocellular carcinoma cells in vitro using a novel monoclonal antibodybased gene delivery system [J]. Hepatology, 1999; 29(1)∶82.
  9. 9. Moradpour D, Compagnon B, Wilson BE, et al. Specific targeting of human hepatocellular carcinoma cells by immunoliposomes in vitro [J]. Hepatology, 1995; 22(5)∶1527.
  10. 10. Cotten M, LangleRouault F, Kirlappos H, et al. Transferrinpolycationmediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels [J]. Proc Natl Acad Sci USA, 1990; 87(11)∶4033.
  11. 11. Curiel DT, Agarwal S, Wagner E, et al. Adenovirus enhancement of transferrinpolylysinemediated gne delivery [J]. Proc Natl Acad Sci USA, 1991; 88(19)∶8850.
  12. 12. Moradpour D, Schauer JI, Zurawski VR, et al. Efficient gene transfer into mammalian cells with cholesterylspermidine [J]. Biochem Biophys Res Commun, 1996; 221(1)∶82.
  13. 13. Plank C , Mechtler K, Szoka FC Jr, et al. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery [J]. Hum Gene Ther, 1996; 7(12)∶1437.
  14. 14. Zern MA, Kresina TF. Hepatic drug delivery and gene therapy [J]. Hepatology, 1997; 25(2)∶484.
  15. 15. Somia NV, Zoppe M, Verma IM. Generation of targeted retroviral vectors by using singlechain variable fragment: an approach to in vivo gene delivery [J]. Proc Natl Acad Sci USA,1995; 92(16)∶7570.
  16. 16. Yang Y, Nunes FA, Bernencsi K, et al. Cellular immunity to viral antigens limits E1deleted adenovirus for gene therapy [J]. Proc Natl Acad Sci USA, 1994; 91(10)∶4407.
  17. 17. Engelhardt JF, Ye X, Doranz B, et al.Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver [J]. Proc Natl Acad Sci USA, 1994; 91(13)∶6196.
  18. 18. Ruoslahti E. Alphafetoprotein in cancer and fetal development [J] Adv Cancer Res,1979; 29∶275.
  19. 19. Xu GW, Sun ZT, Forrester K, et al. Tissuespecific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by retroviralmediated transfer of the wildtype P53 gene [J]. Hepatology, 1996; 24(5)∶1264.
  20. 20. Ido A, Nakata K, Kato Y, et al. Gene therapy for hepatoma cells using a retrovirus vector carring herpes simplex virus thymidine kinase gene under the control of human alphafetoprotein gene promoter [J]. Cancer Res, 1995; 55(14)∶3105.
  21. 21. Kanai F, Shiratori Y, Yoshida Y, et al. Gene therapy for alphafetoproteinproducing human hepatoma cells by adenovirusmediated transfer of the herpes simplex virus thymidine kinase gene [J]. Hepatology, 1996; 23(6)∶1359.
  22. 22. Su H, Lu R, Chang JC, et al. Tissuespecific expression of herpes simplex virus thymidine kinase gene delivered by adenoassociated virus inhibits the growth of human hepatocellular carcinoma in athymic mice [J]. Proc Natl Acad Sci USA, 1997; 94(25)∶13891.
  23. 23. Ohguchi S, Nakatsukasa H, Higashi T, et al. Expression of αfetoprotein and albumin genes in human hepatocellular carcinomas: limitations in the application of the genes for targeting human hepatocellular carcinoma in gene therapy [J]. Hepatology, 1998; 27(2)∶599.
  24. 24. Vollmer CM Jr, Eilber FC, Butterfield LH, et al. Alphafetoproteinspecific genetic immunotherapy for hepatocellular carcinoma [J]. Cancer Res,1999; 59(13)∶3064.
  25. 25. Gordon EM, Liu PX, Chen ZH, et al. Inhibition of metastatic tumor growth in nude mice by portal vein infusions of matrixtargeted retroviral vectors bearing a cytocidal cyclin G1 construct [J]. Cancer Res, 2000; 60(13)∶3343.