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.
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Literature Cited
Roth JA et al. Semin Oncol 1998; 25(3, Suppl. 8):33–37.
Lisziewicz J, Sun D, Lisziewicz A et al. Gene Ther 1995; 2:218–222.
Aalto Setala K, Vuorio E. Ann Med 1997; 29:549–551.
Farhood H, Serbina N, Huang L. Biochim Biophys Acta 1995; 1235:289–295.
Scheule RK et al. Hum Gene Ther 1997; 8:689–707.
Filion MC, Phililips NC. Biochim Bhiophys Acta 1997; 1329:345–356.
Dokka S, Toledo D, Shi X et al. Pharm Res 2000; 17:521–525.
Aberle AM et al. Biochemistry 1998; 37:6533–6540.
Tang F, Hughes JA. Bioconjug Chem 1999; 10:791–796.
Bai HZ et al. Ann Thorac Surg 1998; 66:814–819.
Dalesandro J et al. J Thorac Cardiovasc Surg 1996; 111:416–421.
Yano M, Hiratsuka M, Mora BN et al. Ann Thorac Surg 1999; 68:1810–1814.
Boasquevisque CH et al. J Thorac Cardiovasc Surg 1999; 117:8–14.
Rosenthal FM et al. in Vivo 1997; 11:210–208.
Xu Y, Szoka FC, Jr. Biochemistry 1996; 35:5616–5623.
Khaw BA, Torchilin VP, Vural I et al. Nat Med 1995; 1:1195–1198.
Khaw BA, Narula J, Vural I et al. Int J Pharm 1998; 162:71–76.
Khaw BA, Vural I, DaSilva J et al. STP Pharma Sci 2000; 10:279–283.
Khaw BA, Beller GA, Haber E et al. J Clin Invest 1976; 58:439–446.
Khaw BA, Fallon JT, Beller GA et al. Circulation 1979; 60:1527–1531.
Torchilin VP, Ivanov NN, Klibanov AL et al. in Liposomes as Drug Carriers G Gregoriadis (ed.), Wiley, Avon, UK, 1988, pp. 63–74.
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.
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.
Khaw BA, DaSilva J, Vural I et al. J Control Release Submitted.
Felgner PL, Ringold GM. Nature 1989; 337:387–388.
Prazeres DMF, Schluep T, Cooney C. J Chromatogr 1998; 806:31–45.
Khaw BA, Beller GA, Haber E et al. J Clin Invest 1976; 58:439–446.
Khaw BA, Scott J, Fallon JT et al. Science 1982; 217:1050–1053.
Torchilin VP, Narula J, Halpern E et al. Biochim Biophys Acta 1996; 1279:75–83.
Torchilin VP et al. J Control Release 1994; 28:45–58.
Papa S, Scacco S, Schliebs M et al. Mol Aspects Med 1996; 17:513–563.
Wallace DC. Science 1999; 283:1482–1488.
Holt IJ, Harding AE, Morgan-Hughes JA. Nature 1988; 331:717–719.
Harding AE. TINS 1991; 14:132–138.
Sperl W. Wien Klin Wochenschr 1997; 109:93–99.
Seibel P, Trappe J, Villani G et al. Nucleic Acids Res 1995; 23:10–17.
Chrzanowska-Lightowlers ZMA, Lightowlers RN, Turnbull DM. Gene Ther 1995; 2:311–316.
Jacobs HT. J Mol Evol 1991; 32:333–339.
Kagawa Y, Hayashi JI. Gene Ther 1997; 4:6–10.
Collombet JC, Coutelle C. Mol Med Today 1998; 4:31–38.
Butow RT, Fox TD. Trends Biochem Sci 1990; 15:465–468.
Collombet JM, Wheeler VC, Vogel F et al. J Biol Chem 1997; 272:5342–5347.
Vestweber D, Schatz G. Nature (London) 1989; 338:170–172.
Zabner J, Fasbender AJ, Moninger T et al. J Biol Chem 1995; 270:18997–19007.
Chin DJ, Green GA, Zon G et al. New Biol 1990; 2:1091–1100.
Murphy MP. Biochim Biophys Acta 1989; 977:123–141.
Chen LB et al. Cold Spring Harb Symp Quant Biol 1982; 46:141–155.
Rideout D, Bustamante A, Patel J. Int J Cancer 1994; 57:247–253.
Lampidis TJ, Hasin Y, Weiss MJ et al. Biomed Pharmacother 1985; 39:220–226.
Weiss MJ et al. Proc Natl Acad Sci USA 1987; 84:5444–5448.
Weissig V et al. Pharm Res 1998; 15:334–337.
Weissig V, Torchilin VP. Current Pharm Biotech 2000; 1:325–346.
Weissig V, Mögel H-J, Wahab M et al. Proc Int Symp Control Rel Bioact Mater 1998; 25:312–313.
Lasch J. Biol Chem 1999; 380:647–652.
Hovius R, Lambrecht H, Nicolay K et al. Biochim Biophys Acta 1990; 1021:217–226.
Daum G. Biochim Biophys Acta 1985; 822:1–42.
Weissig V, Lizano C, Torchilin VP. Drug Deliv 2000; 7:1–5.
Chappell JB, Hansford RG. in Subcellular Components: Preparation and Fractionation, GD Birnie (ed.), Butterworths, London, 1972, pp. 77–91.
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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
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DOI: https://doi.org/10.1023/A:1022936024061