Abstract
The self-assembly of supramolecular complexes of nucleic acids and polymers is of relevance to several biological processes including viral and chromatin formation as well as gene therapy vector design. We now show that template polymerization facilitates condensation of DNA into particles that are <150 nm in diameter. Inclusion of a poly(ethylene glycol)-containing monomer prevents aggregation of these particles. The DNA within the particles remains biologically active and can express foreign genes in cells. The formation or breakage of covalent bonds has until now not been employed to compact DNA into artificial particles.
Full Text
The Full Text of this article is available as a PDF (174.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arscott P. G., Li A. Z., Bloomfield V. A. Condensation of DNA by trivalent cations. 1. Effects of DNA length and topology on the size and shape of condensed particles. Biopolymers. 1990;30(5-6):619–630. doi: 10.1002/bip.360300514. [DOI] [PubMed] [Google Scholar]
- Bloomfield V. A. DNA condensation. Curr Opin Struct Biol. 1996 Jun;6(3):334–341. doi: 10.1016/s0959-440x(96)80052-2. [DOI] [PubMed] [Google Scholar]
- Budker V., Hagstrom J. E., Lapina O., Eifrig D., Fritz J., Wolff J. A. Protein/amphipathic polyamine complexes enable highly efficient transfection with minimal toxicity. Biotechniques. 1997 Jul;23(1):139, 142-7. doi: 10.2144/97231rr02. [DOI] [PubMed] [Google Scholar]
- Dunlap D. D., Maggi A., Soria M. R., Monaco L. Nanoscopic structure of DNA condensed for gene delivery. Nucleic Acids Res. 1997 Aug 1;25(15):3095–3101. doi: 10.1093/nar/25.15.3095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katayose S., Kataoka K. Water-soluble polyion complex associates of DNA and poly(ethylene glycol)-poly(L-lysine) block copolymer. Bioconjug Chem. 1997 Sep-Oct;8(5):702–707. doi: 10.1021/bc9701306. [DOI] [PubMed] [Google Scholar]
- Kolb V., Orgel L. E. Oligonucleotides as probes for studying polymerization reactions in dilute aqueous solution. J Mol Evol. 1994;38:433–437. [PubMed] [Google Scholar]
- Kosturko L. D., Dattagupta N., Crothers D. M. Selective repression of transcription by base sequence specific synthetic polymers. Biochemistry. 1979 Dec 25;18(26):5751–5756. doi: 10.1021/bi00593a001. [DOI] [PubMed] [Google Scholar]
- Pazin M. J., Kadonaga J. T. What's up and down with histone deacetylation and transcription? Cell. 1997 May 2;89(3):325–328. doi: 10.1016/s0092-8674(00)80211-1. [DOI] [PubMed] [Google Scholar]
- Porschke D. Dynamics of DNA condensation. Biochemistry. 1984 Oct 9;23(21):4821–4828. doi: 10.1021/bi00316a002. [DOI] [PubMed] [Google Scholar]
- Reimer D. L., Zhang Y., Kong S., Wheeler J. J., Graham R. W., Bally M. B. Formation of novel hydrophobic complexes between cationic lipids and plasmid DNA. Biochemistry. 1995 Oct 3;34(39):12877–12883. doi: 10.1021/bi00039a050. [DOI] [PubMed] [Google Scholar]
- Sebestyén M. G., Ludtke J. J., Bassik M. C., Zhang G., Budker V., Lukhtanov E. A., Hagstrom J. E., Wolff J. A. DNA vector chemistry: the covalent attachment of signal peptides to plasmid DNA. Nat Biotechnol. 1998 Jan;16(1):80–85. doi: 10.1038/nbt0198-80. [DOI] [PubMed] [Google Scholar]
- Shimizu T., Takao T., Hozumi K., Nunomura K., Ohta S., Shimonishi Y., Ikegami S. Structure of a covalently cross-linked form of core histones present in the starfish sperm. Biochemistry. 1997 Oct 7;36(40):12071–12079. doi: 10.1021/bi970922n. [DOI] [PubMed] [Google Scholar]
- Tang M. X., Szoka F. C. The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes. Gene Ther. 1997 Aug;4(8):823–832. doi: 10.1038/sj.gt.3300454. [DOI] [PubMed] [Google Scholar]
- Wolfert M. A., Schacht E. H., Toncheva V., Ulbrich K., Nazarova O., Seymour L. W. Characterization of vectors for gene therapy formed by self-assembly of DNA with synthetic block co-polymers. Hum Gene Ther. 1996 Nov 10;7(17):2123–2133. doi: 10.1089/hum.1996.7.17-2123. [DOI] [PubMed] [Google Scholar]
- Zhang G., Vargo D., Budker V., Armstrong N., Knechtle S., Wolff J. A. Expression of naked plasmid DNA injected into the afferent and efferent vessels of rodent and dog livers. Hum Gene Ther. 1997 Oct 10;8(15):1763–1772. doi: 10.1089/hum.1997.8.15-1763. [DOI] [PubMed] [Google Scholar]