often even much higher) in order to be comparable to the commercial polymeric
gene delivery agents (usually prepared at N:P ratios of less than 10).
Unfortunately, in all these cases, there are nevertheless problems in defining
clear structure–activity relationships and explaining the apparent discrepancies
between the behavior of the polyplexes in vitro and their poor performance
in vivo. It is highly probable that the actual morphology of the polyplexes deviates
from the expected structure (core–shell, etc.).
Moreover, it should not be forgotten that, since gene therapy using
oligonucleotides such as antisense oligodeoxynucleotides (ODN); short RNA
molecules such as small interfering RNA (siRNA), micro-RNA (miRNA), and short
hairpin RNA (shRNA); or a DNAzyme that leads to a reduction in target/protein
activity [240] takes more and more importance, the study of the complexes of these
oligomeric materials with polycations is of increasing interest. Moreover, the application of DNA–polymer complexes is not limited to gene therapy and they also find use
as DNA vaccines and biosensors.
Some challenges remain concerning the synthesis and structure of these
polymers; for instance, finding new biocompatible polymers other than PEG.
Moreover, in order to define clear structure–function relationships, it is necessary
to use new polymerization techniques to obtain well-defined materials rather than
randomized polymers [241]. Similarly, more architecturally controlled
macromolecules such as dendronized polymers appear to be promising prospects
in the field of polycations for gene delivery [242].
References
1. Kundu PP, Sharma V (2008) Synthetic polymeric vectors in gene therapy. Curr Opin Solid
State Mater Sci 12:89–102
2. Wong SY, Pelet JM, Putnam D (2007) Polymer systems for gene delivery–past, present, and
future. Prog Polym Sci 32:799–837
3. Dubruel P, Schacht E (2006) Vinyl polymers as non-viral gene delivery carriers: current
status and prospects. Macromol Biosci 6:789–810
4. Kabanov AV, Felgner PL, Seymour LW (eds) (1998) Self-assembling complexes for gene
delivery. Wiley, New York
5. Shcharbin DG, Klajnert B, Bryszewska M (2009) Dendrimers in gene transfection. Biochemistry 74:1070–1079
6. Dufe `s C, Uchegbu IF, Scha ¨tzlein AG (2005) Dendrimers in gene delivery. Adv Drug Deliv
Rev 57:2177–2202
7. Ainalem M-L, Nylander T (2011) DNA condensation using cationic dendrimers–morphology
and supramolecular structure of formed aggregates. Soft Matter 7:4577–4594
8. Guillot-Nieckowski M, Eisler S, Diederich F (2007) Dendritic vectors for gene transfection.
New J Chem 31:1111–1127
9. Paleos CM, Tsiourvas D, Sideratou Z (2007) Molecular engineering of dendritic polymers
and their application as drug and gene delivery systems. Mol Pharm 4:169–188
10. Fischer W, Caldero ´n M, Haag R (2010) Hyperbranched polyamines for transfection. Top
Curr Chem 296:95–129
Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors
183
gene delivery agents (usually prepared at N:P ratios of less than 10).
Unfortunately, in all these cases, there are nevertheless problems in defining
clear structure–activity relationships and explaining the apparent discrepancies
between the behavior of the polyplexes in vitro and their poor performance
in vivo. It is highly probable that the actual morphology of the polyplexes deviates
from the expected structure (core–shell, etc.).
Moreover, it should not be forgotten that, since gene therapy using
oligonucleotides such as antisense oligodeoxynucleotides (ODN); short RNA
molecules such as small interfering RNA (siRNA), micro-RNA (miRNA), and short
hairpin RNA (shRNA); or a DNAzyme that leads to a reduction in target/protein
activity [240] takes more and more importance, the study of the complexes of these
oligomeric materials with polycations is of increasing interest. Moreover, the application of DNA–polymer complexes is not limited to gene therapy and they also find use
as DNA vaccines and biosensors.
Some challenges remain concerning the synthesis and structure of these
polymers; for instance, finding new biocompatible polymers other than PEG.
Moreover, in order to define clear structure–function relationships, it is necessary
to use new polymerization techniques to obtain well-defined materials rather than
randomized polymers [241]. Similarly, more architecturally controlled
macromolecules such as dendronized polymers appear to be promising prospects
in the field of polycations for gene delivery [242].
References
1. Kundu PP, Sharma V (2008) Synthetic polymeric vectors in gene therapy. Curr Opin Solid
State Mater Sci 12:89–102
2. Wong SY, Pelet JM, Putnam D (2007) Polymer systems for gene delivery–past, present, and
future. Prog Polym Sci 32:799–837
3. Dubruel P, Schacht E (2006) Vinyl polymers as non-viral gene delivery carriers: current
status and prospects. Macromol Biosci 6:789–810
4. Kabanov AV, Felgner PL, Seymour LW (eds) (1998) Self-assembling complexes for gene
delivery. Wiley, New York
5. Shcharbin DG, Klajnert B, Bryszewska M (2009) Dendrimers in gene transfection. Biochemistry 74:1070–1079
6. Dufe `s C, Uchegbu IF, Scha ¨tzlein AG (2005) Dendrimers in gene delivery. Adv Drug Deliv
Rev 57:2177–2202
7. Ainalem M-L, Nylander T (2011) DNA condensation using cationic dendrimers–morphology
and supramolecular structure of formed aggregates. Soft Matter 7:4577–4594
8. Guillot-Nieckowski M, Eisler S, Diederich F (2007) Dendritic vectors for gene transfection.
New J Chem 31:1111–1127
9. Paleos CM, Tsiourvas D, Sideratou Z (2007) Molecular engineering of dendritic polymers
and their application as drug and gene delivery systems. Mol Pharm 4:169–188
10. Fischer W, Caldero ´n M, Haag R (2010) Hyperbranched polyamines for transfection. Top
Curr Chem 296:95–129
Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors
183