Skip to main content
Log in

Intracellular Targets for DNA Delivery: Nuclei and Mitochondria

  • Published:
Somatic Cell and Molecular Genetics

Abstract

All discussions on the intracellular delivery of DNA are based on a seemingly evident assumption that the key task is to bring the intact DNA into the cell cytoplasmic compartment, and then the DNA will find its way to a right place. The nuclear genome is usually considered to be this “right place.” However, until recently, in numerous experiments on the intracellular DNA delivery, it has been almost completely neglected that cells contain another genome, the mitochondrial one. And, in many cases, this genome should become a therapeutic target. Being delivered inside the cell, DNA actually has two ways to go—to nuclei and to mitchondria, and the proper choice between these two ways may be decisive for the success of gene therapy. Certainly, nuclear DNA delivery is far more advanced than mitochondrial delivery one. In addition, free DNA from the cytoplasm has a strong tendency to spontaneously associate with the nuclear genome. Mitochondria as a target for DNA have much less accessibility, still remaining an important site to reach. Whereas the nuclear delivery of DNA is under active investigation and just awaits better protocols to be elaborated, practically applicable mitochondrial DNA delivery is at its early stage and must be developed almost from scratch. In our studies on intracellular DNA delivery, we have attempted to develop new protocols for targeting DNA to nuclei and to mitochondria. In this chapter we provide a brief description of our recent experiments in both of these important areas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Literature Cited

  1. Roth JA et al. Semin Oncol 1998; 25(3, Suppl. 8):33–37.

    Google Scholar 

  2. Lisziewicz J, Sun D, Lisziewicz A et al. Gene Ther 1995; 2:218–222.

    Google Scholar 

  3. Aalto Setala K, Vuorio E. Ann Med 1997; 29:549–551.

    Google Scholar 

  4. Farhood H, Serbina N, Huang L. Biochim Biophys Acta 1995; 1235:289–295.

    Google Scholar 

  5. Scheule RK et al. Hum Gene Ther 1997; 8:689–707.

    Google Scholar 

  6. Filion MC, Phililips NC. Biochim Bhiophys Acta 1997; 1329:345–356.

    Google Scholar 

  7. Dokka S, Toledo D, Shi X et al. Pharm Res 2000; 17:521–525.

    Google Scholar 

  8. Aberle AM et al. Biochemistry 1998; 37:6533–6540.

    Google Scholar 

  9. Tang F, Hughes JA. Bioconjug Chem 1999; 10:791–796.

    Google Scholar 

  10. Bai HZ et al. Ann Thorac Surg 1998; 66:814–819.

    Google Scholar 

  11. Dalesandro J et al. J Thorac Cardiovasc Surg 1996; 111:416–421.

    Google Scholar 

  12. Yano M, Hiratsuka M, Mora BN et al. Ann Thorac Surg 1999; 68:1810–1814.

    Google Scholar 

  13. Boasquevisque CH et al. J Thorac Cardiovasc Surg 1999; 117:8–14.

    Google Scholar 

  14. Rosenthal FM et al. in Vivo 1997; 11:210–208.

    Google Scholar 

  15. Xu Y, Szoka FC, Jr. Biochemistry 1996; 35:5616–5623.

    Google Scholar 

  16. Khaw BA, Torchilin VP, Vural I et al. Nat Med 1995; 1:1195–1198.

    Google Scholar 

  17. Khaw BA, Narula J, Vural I et al. Int J Pharm 1998; 162:71–76.

    Google Scholar 

  18. Khaw BA, Vural I, DaSilva J et al. STP Pharma Sci 2000; 10:279–283.

    Google Scholar 

  19. Khaw BA, Beller GA, Haber E et al. J Clin Invest 1976; 58:439–446.

    Google Scholar 

  20. Khaw BA, Fallon JT, Beller GA et al. Circulation 1979; 60:1527–1531.

    Google Scholar 

  21. Torchilin VP, Ivanov NN, Klibanov AL et al. in Liposomes as Drug Carriers G Gregoriadis (ed.), Wiley, Avon, UK, 1988, pp. 63–74.

    Google Scholar 

  22. Khaw BA, Vural I, Torchilin VP et al. In Proc. 23rd International Symposium on Controlled Release of Bioactive Materials, Kyoto, Japan, Controlled Release Society, 1996, pp. 135–136.

  23. Sambrook D, Fritsch EF, Maniatis T. Molecular Cloning: A Laboratory Manual, 2nd edn., Cold Spring Harbor Laboratory Press, Cold Spring Harbor Laboratory, New York, 1989.

    Google Scholar 

  24. Khaw BA, DaSilva J, Vural I et al. J Control Release Submitted.

  25. Felgner PL, Ringold GM. Nature 1989; 337:387–388.

    Google Scholar 

  26. Prazeres DMF, Schluep T, Cooney C. J Chromatogr 1998; 806:31–45.

    Google Scholar 

  27. Khaw BA, Beller GA, Haber E et al. J Clin Invest 1976; 58:439–446.

    Google Scholar 

  28. Khaw BA, Scott J, Fallon JT et al. Science 1982; 217:1050–1053.

    Google Scholar 

  29. Torchilin VP, Narula J, Halpern E et al. Biochim Biophys Acta 1996; 1279:75–83.

    Google Scholar 

  30. Torchilin VP et al. J Control Release 1994; 28:45–58.

    Google Scholar 

  31. Papa S, Scacco S, Schliebs M et al. Mol Aspects Med 1996; 17:513–563.

    Google Scholar 

  32. Wallace DC. Science 1999; 283:1482–1488.

    Google Scholar 

  33. Holt IJ, Harding AE, Morgan-Hughes JA. Nature 1988; 331:717–719.

    Google Scholar 

  34. Harding AE. TINS 1991; 14:132–138.

    Google Scholar 

  35. Sperl W. Wien Klin Wochenschr 1997; 109:93–99.

    Google Scholar 

  36. Seibel P, Trappe J, Villani G et al. Nucleic Acids Res 1995; 23:10–17.

    Google Scholar 

  37. Chrzanowska-Lightowlers ZMA, Lightowlers RN, Turnbull DM. Gene Ther 1995; 2:311–316.

    Google Scholar 

  38. Jacobs HT. J Mol Evol 1991; 32:333–339.

    Google Scholar 

  39. Kagawa Y, Hayashi JI. Gene Ther 1997; 4:6–10.

    Google Scholar 

  40. Collombet JC, Coutelle C. Mol Med Today 1998; 4:31–38.

    Google Scholar 

  41. Butow RT, Fox TD. Trends Biochem Sci 1990; 15:465–468.

    Google Scholar 

  42. Collombet JM, Wheeler VC, Vogel F et al. J Biol Chem 1997; 272:5342–5347.

    Google Scholar 

  43. Vestweber D, Schatz G. Nature (London) 1989; 338:170–172.

    Google Scholar 

  44. Zabner J, Fasbender AJ, Moninger T et al. J Biol Chem 1995; 270:18997–19007.

    Google Scholar 

  45. Chin DJ, Green GA, Zon G et al. New Biol 1990; 2:1091–1100.

    Google Scholar 

  46. Murphy MP. Biochim Biophys Acta 1989; 977:123–141.

    Google Scholar 

  47. Chen LB et al. Cold Spring Harb Symp Quant Biol 1982; 46:141–155.

    Google Scholar 

  48. Rideout D, Bustamante A, Patel J. Int J Cancer 1994; 57:247–253.

    Google Scholar 

  49. Lampidis TJ, Hasin Y, Weiss MJ et al. Biomed Pharmacother 1985; 39:220–226.

    Google Scholar 

  50. Weiss MJ et al. Proc Natl Acad Sci USA 1987; 84:5444–5448.

  51. Weissig V et al. Pharm Res 1998; 15:334–337.

    Google Scholar 

  52. Weissig V, Torchilin VP. Current Pharm Biotech 2000; 1:325–346.

    Google Scholar 

  53. Weissig V, Mögel H-J, Wahab M et al. Proc Int Symp Control Rel Bioact Mater 1998; 25:312–313.

    Google Scholar 

  54. Lasch J. Biol Chem 1999; 380:647–652.

    Google Scholar 

  55. Hovius R, Lambrecht H, Nicolay K et al. Biochim Biophys Acta 1990; 1021:217–226.

    Google Scholar 

  56. Daum G. Biochim Biophys Acta 1985; 822:1–42.

    Google Scholar 

  57. Weissig V, Lizano C, Torchilin VP. Drug Deliv 2000; 7:1–5.

    Google Scholar 

  58. Chappell JB, Hansford RG. in Subcellular Components: Preparation and Fractionation, GD Birnie (ed.), Butterworths, London, 1972, pp. 77–91.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torchilin, V.P., Khaw, BA. & Weissig, V. Intracellular Targets for DNA Delivery: Nuclei and Mitochondria. Somat Cell Mol Genet 27, 49–64 (2002). https://doi.org/10.1023/A:1022936024061

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022936024061

Keywords

Navigation