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  • Review Article
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Polymers for gene delivery across length scales

Abstract

A number of human diseases stem from defective genes. One approach to treating such diseases is to replace, or override, the defective genes with normal genes, an approach called 'gene therapy'. However, the introduction of correctly functioning DNA into cells is a non-trivial matter, and cells must be coaxed to internalize, and then use, the DNA in the desired manner. A number of polymer-based synthetic systems, or 'vectors', have been developed to entice cells to use exogenous DNA. These systems work across the nano, micro and macro length scales, and have been under continuous development for two decades, with varying degrees of success. The design criteria for the construction of more-effective delivery vectors at each length scale are continually evolving. This review focuses on the most recent developments in polymer-based vector design at each length scale.

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Figure 1: Length scales associated with DNA delivery vectors.
Figure 2: General structures of the first combinatorial libraries synthesized to enhance DNA delivery.
Figure 3: Virus/polymer conjugates to reduce virus immunogenicity, improve biodistribution profile, and alter tropism.
Figure 4: Degradation of polymeric microspheres as a function of pH.
Figure 5

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References

  1. Luo, D. & Saltzman, W. M. Synthetic DNA delivery systems. Nature Biotechnol. 18, 33–37 (2000).

    CAS  Google Scholar 

  2. Schaffer, D. V. & Lauffenburger, D. A. Targeted synthetic gene delivery vectors. Curr. Opin. Mol. Ther. 2, 155–161 (2000).

    CAS  Google Scholar 

  3. Mahato, R. I., Smith, L. C. & Rolland, A. Pharmaceutical perspectives of nonviral gene therapy. Adv. Genet. 41, 95–156 (1999).

    CAS  Google Scholar 

  4. Demeneix, B., Hassani, Z. & Behr, J. P. Towards multifunctional synthetic vectors Curr. Gene Ther. 4, 445–455 (2004).

    CAS  Google Scholar 

  5. Roth, C. M. & Sundaram, S. Engineering synthetic vectors for improved DNA delivery: insights from intracellular pathways. Annu. Rev. Biomed. Eng. 6, 397–426 (2004).

    CAS  Google Scholar 

  6. Mahato, R. I. Non-viral peptide-based approaches to gene delivery J. Drug Target. 7, 249–268 (1999).

    CAS  Google Scholar 

  7. Schatzlein, A. G. Non-viral vectors in cancer gene therapy: principles and progress. Anticancer Drugs 12, 275–304 (2001).

    CAS  Google Scholar 

  8. Wiethoff, C. M. & Middaugh, C. R. Barriers to nonviral gene delivery J. Pharm. Sci. 92, 203–217 (2003).

    CAS  Google Scholar 

  9. Cho, Y. W., Kim, J. D. & Park, K. Polycation gene delivery systems: escape from endosomes to cytosol. J. Pharm. Pharmacol. 55, 1–734 (2003).

    Google Scholar 

  10. Pannier, A. K. & Shea, L. D. Controlled release systems for DNA delivery. Mol. Ther. 10, 19–26 (2004).

    CAS  Google Scholar 

  11. Molas, M. et al. Receptor-mediated gene transfer vectors: progress towards genetic pharmaceuticals. Curr. Gene Ther. 3, 468–485 (2003).

    CAS  Google Scholar 

  12. Roy, I. & Gupta, M. N. Smart polymeric materials: emerging biochemical applications. Chem. Biol. 10, 1161–1171 (2003).

    CAS  Google Scholar 

  13. Kakizawa, Y. & Kataoka, K. Block copolymer micelles for delivery of gene and related compounds. Adv. Drug Deliv. Rev. 54, 203–222 (2002).

    CAS  Google Scholar 

  14. 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. 4, 823–832 (1997).

    CAS  Google Scholar 

  15. Dubruel, P. et al. Synthetic polyamines as vectors for gene delivery. Polym. Int. 51, 948–957 (2002).

    CAS  Google Scholar 

  16. Merdan, T., Kopecek, J. & Kissel, T. Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Adv. Drug Deliv. Rev. 54, 715–758 (2002).

    CAS  Google Scholar 

  17. Murphy, J. E. et al. A combinatorial approach to the discovery of efficient cationic peptoid reagents for gene therapy. Proc. Natl Acad. Sci. USA 95, 1517–1522 (1998).

    CAS  Google Scholar 

  18. Lenssen, K., Jantscheff, P., von Kiedrowski, G. & Massing, U. Combinatorial synthesis of new cationic lipids and high-throughput screening of their transfection properties. ChemBioChem 3, 852–858 (2002).

    CAS  Google Scholar 

  19. Lynn, D. M., Anderson, D. G., Putnam, D. & Langer, R. Accelerated discovery of synthetic transfection vectors: parallel synthesis and screening of a degradable polymer library. J. Am. Chem. Soc. 123, 8155–8156 (2001).

    CAS  Google Scholar 

  20. Anderson, D. G., Lynn, D. M. & Langer, R. Semi-automated synthesis and screening of a large library of degradable cationic polymers for gene delivery. Angew. Chem. Int. Edn 42, 3153–3158 (2003).

    CAS  Google Scholar 

  21. Akinc, A., Lynn, D. M., Anderson, D. G. & Langer. R. Parallel synthesis and biophysical characterization of a degradable polymer library for gene delivery. J. Am. Chem. Soc. 125, 5316–5323 (2003).

    CAS  Google Scholar 

  22. Akinc, A., Anderson, D. G., Lynn, D. M. & Langer, R. Synthesis of poly(β-amino ester)s optimized for highly effective gene delivery. Bioconjug. Chem. 14, 979–988 (2003).

    CAS  Google Scholar 

  23. Anderson, D. G. et al. A polymer library approach to suicide gene therapy for cancer. Proc. Natl Acad. Sci. USA 101, 16028–16033 (2004).

    CAS  Google Scholar 

  24. Mammen, M., Dahmann, G. & Whitesides, G. Effective inhibitors of hemagglutination by influenze virus synthesized from polymers having active ester groups. Insight in mechanism of inhibition. J. Med. Chem. 38, 4179–4190 (1995).

    CAS  Google Scholar 

  25. Godwin, A., Hartenstein, M., Müller, A. & Brocchini, S. Synthesis of a polymeric precursor by ATRP for conversion to polymer-drug conjugates. Am. Chem. Soc. Polym. Chem. Div. 41, 1002–1003 (2000).

    CAS  Google Scholar 

  26. Godwin, A., Hartenstein, M., Müller, A. & Brocchini, S. Narrow molecular weight distribution precursors for polymer-drug conjugates. Angew. Chem. Int. Edn 40, 594–597 (2001).

    CAS  Google Scholar 

  27. Pedone, E., Li, X., Koseva, N., Alpar, O. & Brocchini, S. An information rich biomedical polymer library. J. Mater. Chem. 13, 2825–2837 (2003).

    CAS  Google Scholar 

  28. Batz, H., Franzmann, G. & Ringsdorf, H. Model reactions for synthesis of pharmacologically active polymers by way of monomeric and polymeric reactive esters. Angew Chem Int. Edn Engl. 11, 1103–1104 (1972).

    CAS  Google Scholar 

  29. Putnam, D. & Kopecek, J. Polymer conjugates with anticancer activity. Adv. Polymer Sci. 122, 55–123 (1995).

    CAS  Google Scholar 

  30. Ferruti, P., Betellini, A. & Fere, A. High polymers of acrylic and methacrylic esters of N-hydroxysuccinimide as polyacrylamide and polymethacrylamide precursors. Polymer 13, 462–464 (1972).

    CAS  Google Scholar 

  31. Davis, F. F. The origin of pegnology. Adv. Drug. Del. Rev. 54, 457–458 (2002).

    CAS  Google Scholar 

  32. MacKay, J. A., Deen, D. F. & Szoka, F. C. Jr Distribution in brain of liposomes after convection enhanced delivery; modulation by particle charge, particle diameter, and presence of steric coating. Brain Res 1035, 139–153 (2005).

    CAS  Google Scholar 

  33. Tsubery, H., Mironchik, M., Fridkin, M. & Shechter, Y. Prolonging the action of protein and peptide drugs by a novel approach of reversible polyethylene glycol modification. J. Biol. Chem. 279, 38118–38124 (2004).

    CAS  Google Scholar 

  34. Alemany, R., Suzuki, K. & Curiel, D. T. Blood clearance rates of adenovirus type 5 in mice. J. Gen. Virol. 81, 2605–2609 (2000).

    CAS  Google Scholar 

  35. Chillon, M., Lee, J. H., Fasbender, A. & Welsh, M. J. Adenovirus complexed with polyethylene glycol and cationic lipid is shielded from neutralizing antibodies in vitro. Gene Ther. 5, 995–1002 (1998).

    CAS  Google Scholar 

  36. O'Riordan, C. R. et al. PEGylation of adenovirus with retention of infectivity and protection from neutralizing antibody in vitro and in vivo. Hum. Gene Ther. 10, 1349–1358 (1999).

    CAS  Google Scholar 

  37. Croyle, M. A., Yu, Q.-C. & Wilson, J. M. Development of a rapid method for the PEGylation of adenoviruses with enhanced transduction and improved stability under harsh storage conditions. Hum. Gene Ther. 11, 1713–1722 (2000).).

    CAS  Google Scholar 

  38. Green, N. K. et al. Extended plasma circulation time and decreased toxicity of polymer-coated adenovirus. Gene Ther. 11, 1256–1263 (2004).

    CAS  Google Scholar 

  39. Wickham, T. J., Roelvink, P., Brough, D. E. & Kovesdi, I. Adenovirus targeted to heparin-containing receptors increases its gene delivery efficiency to multiple cell types. Nature Biotechnol. 14, 1570–1573 (1996).

    CAS  Google Scholar 

  40. Wickham, T. J. et al. Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins. J. Virol. 71, 8221–8229 (1997).

    CAS  Google Scholar 

  41. Reynolds, P., Dmitriev, I. & Curiel, D. Insertion of an RGD motif into the HI loop of adenovirus fiber protein alters the distribution of transgene expression of the systemically administered vector. Gene Ther. 6, 1336–1339 (1999).

    CAS  Google Scholar 

  42. Lanciotti, J. et al. Targeting adenoviral vectors using heterofunctional polyethylene glycol FGF2 conjugates. Mol. Ther. 8, 99–107 (2003).

    CAS  Google Scholar 

  43. Fisher, K. D. et al. Polymer-coated adenovirus permits efficient retargeting and evades neutralising antibodies. Gene Ther. 8, 341–348 (2001).

    CAS  Google Scholar 

  44. Lee, G. K., Maheshri, N., Kaspar, B. & Schaffer, D. V. PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. Biotechnol. Bioeng. 92, 24–34 (2005).

    CAS  Google Scholar 

  45. Croyle, M. A. et al. PEGylation of a vesicular stomatitis virus G pseudotyped lentivirus vector prevents inactivation in serum. J. Virol. 78, 912–921 (2004).

    CAS  Google Scholar 

  46. Soong, N. W. et al. Molecular breeding of viruses Nature Genet. 25, 436–439 (2000).

    CAS  Google Scholar 

  47. Maheshri, N., Koerber, J. T., Kaspar, B. & Schaffer, D. V. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nature Biotechnol. 24, 198–204 (2006).

    CAS  Google Scholar 

  48. Donnelly, J. J., Wahren, B. & Liu, M. A. DNA vaccines: progress and challenges. J. Immunol. 175, 633–639 (2005).

    CAS  Google Scholar 

  49. Hedley, M. L., Curley, J. & Urban, R. Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses. Nature Med. 4, 365–368 (1998).

    CAS  Google Scholar 

  50. Jones, D. H., Corris, S., McDonald, S., Clegg, J. C. & Farrar, G. H. Poly(D,L-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and mucosal antibody responses to encoded protein after oral administration. Vaccine 15, 814–817 (1997).

    CAS  Google Scholar 

  51. Tabata, I. & Ikada, Y. Phagocytosis of polymer microspheres by macrophages. Adv. Polym. Sci. 94, 107–141 (1990).

    CAS  Google Scholar 

  52. Luby, T. M. et al. Repeated immunization with plasmid DNA formulated in poly(lactide-co-glycolide) microparticles is well tolerated and stimulates durable T cell responses to the tumor-associated antigen cytochrome P450 1B1. Clin. Immunol. 112, 45–53 (2004).

    CAS  Google Scholar 

  53. Crum, C. P. et al. Dynamics of human papillomavirus infection between biopsy and excision of cervical intraepithelial neoplasia: results from the ZYC101a protocol. J. Infect. Dis. 189, 1348–1354 (2004).

    Google Scholar 

  54. Fu, K., Pack, D. W., Klibanov, A. M. & Langer, R. Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres. Pharm. Res. 17, 100–106 (2000).

    CAS  Google Scholar 

  55. Wang, D., Robinson, D. R., Kwon, G. S. & Samuel, J. Encapsulation of plasmid DNA in biodegradable poly(D,L-lactic-co-glycolic acid) microspheres as a novel approach for immunogene delivery. J. Control. Release 57, 9–18 (1999).

    CAS  Google Scholar 

  56. Kaech, S. M. & Ahmed, R. Memory CD8+ T cell differentiation: initial antigen encounter triggers a development program in naïve cells. Nature Immunol. 2, 415–422 (2001).

    CAS  Google Scholar 

  57. Princiotta, M. F. et al. Quantitating protein synthesis, degradation and endogenous antigen processing. Immunity 18, 343–354 (2003).

    CAS  Google Scholar 

  58. Ando, S., Putnam, D., Pack, D. W. & Langer, R. PLGA microspheres containing plasmid DNA: preservation of supercoiled DNA via cryopreparation and carbohydrate stabilization. J. Pharm. Sci. 88, 126–130 (1999).

    CAS  Google Scholar 

  59. Singh, M., Briones, M., Ott, G. & O'Hagan, D. Cationic microparticles: A potent delivery system for DNA vaccines. Proc. Natl Acad. Sci. USA 97, 811–816 (2000).

    CAS  Google Scholar 

  60. O'Hagan D. T., Singh, M. Ulmer J. B. Microparticles for the Delivery of DNA Vaccines. Immunol. Rev. 199, 191–200 (2004).

    CAS  Google Scholar 

  61. Heller, J., Barr, J., Ng, S. Y., Schwach-Abdellaoui, K. & Gurny, R. Poly(ortho esters): synthesis, characterization, properties and uses. Adv. Drug Deliv. Rev. 54, 1015–1039 (2002).

    CAS  Google Scholar 

  62. Cordes, E. H. & Bull, H. G. Mechanism and catalysis for hydrolysis of acetals, ketals, and ortho esters. Chem. Rev. 74, 581–604 (1974).

    CAS  Google Scholar 

  63. Wang, C. et al. Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines. Nature Mater. 3, 190–196 (2004).

    CAS  Google Scholar 

  64. Akinc, A., Anderson, D. G., Lynn, D. M. & Langer, R. Synthesis of poly(beta-amino ester)s optimized for highly effective gene delivery. Bioconjug. Chem 14, 979–88 (2003).

    CAS  Google Scholar 

  65. Lynn, D. M. & Langer R. Degradable Poly(β-amino esters): synthesis, characterization, and self-assembly with plasmid DNA. J. Am. Chem. 122, 10761–10768 (2000).

    CAS  Google Scholar 

  66. Lynn, D. M., Amiji, M. M. & Langer, R. pH-Responsive polymer microspheres: rapid release of encapsulated material within the range of intracellular pH. Angew. Chem. Int. Edn 40, 1707–1710 (2001).

    CAS  Google Scholar 

  67. Little, S. R. et al. Poly(β-amino esters)-containing microparticles enhance the activity of nonviral geneitic vaccines. Proc. Natl Acad. Sci. USA 101, 9534–9539 (2004).

    CAS  Google Scholar 

  68. Oster, C. G. et al. Cationic microparticles consisting of poly(lactide-co-glycolide) and polyethylenimine as carriers systems for parental DNA vaccination. J. Control. Release 104, 359–377 (2005).

    CAS  Google Scholar 

  69. Beer, S. J. et al. Poly (lactic-glycolic) acid copolymer encapsulation of recombinant adenovirus reduces immunogenicity in vivo. Gene Ther. 5, 740–746 (1998).

    CAS  Google Scholar 

  70. Langer, R. & Tirrell, D. A. Designing materials for biology and medicine. Nature 428, 487–492 (2004).

    CAS  Google Scholar 

  71. Niklason, L. E. & Langer, R. Prospects for organ and tissue replacement. J. Am. Med. Assoc. 285, 573–576 (2001).

    CAS  Google Scholar 

  72. Langer, R. New methods of drug delivery. Science 249, 1527–1533 (1992).

    Google Scholar 

  73. Shea, L. D., Smiley, E., Bonadio, J. & Mooney, D. J. DNA delivery from polymer matrices for tissue engineering. Nature Biotechnol. 17, 551–554 (1999).

    CAS  Google Scholar 

  74. Kong, H. J. et al. Non-viral gene delivery regulated by stiffness of cell adhesion substrates. Nature Mater. 4, 460–464 (2005).

    CAS  Google Scholar 

  75. Ziauddin, J. & Sabatini, D. M. Microarrays of cells expressing defined cDNAs. Nature 411, 107–110 (2001).

    CAS  Google Scholar 

  76. Truong-Le, V. L. et al. Gene transfer by DNA-gelatin nanospheres. Arch. Biochem. Biophys. 361, 47–56 (1999).

    CAS  Google Scholar 

  77. Leong, K. W. et al. DNA-polycation nanospheres as non-viral gene delivery vehicles. J. Control. Release 53, 183–193 (1998).

    CAS  Google Scholar 

  78. Zhang, J., Chua, L. S. & Lynn, D. M. Multilayered thin films that sustain the release of functional DNA under physiological conditions. Langmuir 20, 8015–8021 (2004).

    CAS  Google Scholar 

  79. Shen, H., Tan, J. & Saltzman, W. M. Surface-mediated gene transfer from nanocomposites of controlled texture. Nature Mater. 3, 569–574 (2004).

    CAS  Google Scholar 

  80. Segura, T. & Shea, L. D. Surface-tethered DNA complexes for enhanced gene delivery. Bioconjugate Chem. 13, 621–629 (2002).

    CAS  Google Scholar 

  81. Segura, T., Volk, M. J. & Shea, L. D. Substrate-mediated DNA delivery: role of the cationic polymer structure and extent of modification. J. Control. Rel. 93, 69–84 (2003).

    CAS  Google Scholar 

  82. Huang, Y.-C., Riddle, K., Rice, K. G. & Mooney, D. J. Long-term in vivo gene expression via delivery of PEI-DNA condensates from porous polymer scaffolds. Human Gene Ther. 16, 609–617 (2005).

    CAS  Google Scholar 

  83. Huang, Y.-C., Simmons, C., Kaigler, D., Rice, K. G. & Mooney, D. J. Bone regeneration in a rat cranial defect with delivery of PEI-condensed plasmid DNA encoding for bone morphogenetic protein-4 (BMP-4). Gene Ther. 12, 418–426 (2005).

    CAS  Google Scholar 

  84. Cohen-Sacks, H. et al. Delivery and expression of pDNA embedded in collagen matrices. J. Control. Rel. 95, 309–320 (2004).

    CAS  Google Scholar 

  85. Scherer, F., Ulrike, S., Putz, U., Stemberger, A. & Plank, C. Nonviral vector loaded collagen sponges for sustained gene delivery in vitro and in vivo. J. Gene Med. 4, 634–643 (2002).

    CAS  Google Scholar 

  86. Haider, M., Megeed, Z. & Ghandehari, H. Genetically engineered polymers: status and prospects for controlled release. J. Control. Rel. 95, 1–26 (2004).

    CAS  Google Scholar 

  87. Herweijer, H. et al. Time course of gene expression after plasmid DNA gene transfer to the liver. J. Gene Med. 3, 280–291 (2001).

    CAS  Google Scholar 

  88. Miao, C. H. A novel gene expression system: non-viral gene transfer for hemophilia as model systems. Adv. Genet. 54, 143–177 (2005).

    CAS  Google Scholar 

  89. Ivics, Z., Hackett, P. B., Plasterk, R. H. & Izsvak, Z. Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91, 501–510 (1997).

    CAS  Google Scholar 

  90. Hackett, P. B., Ekker, S. C., Largaespada, D. A. & McIvor, R. S. Sleeping Beauty transposon-mediated gene therapy for prolonged expression. Adv. Genet. 54, 189–232 (2005).

    CAS  Google Scholar 

  91. Ginsburg, D. S. & Calos, M. P. Site-specific integration with φC31 integrase for prolonged expression of therapeutic genes. Adv. Genet. 54, 179–187 (2005).

    CAS  Google Scholar 

  92. http://www.wiley.co.uk/genetherapy/clinical

  93. http://www.mgipharma.com

  94. Otten, G. R. et al. Enhanced potency of plasmid DNA microparticle human immunodeficiency virus vaccines in rhesus macaques by using a priming-boosting regimen with recombinant proteins. J. Virol. 79, 8189–8200 (2005).

    CAS  Google Scholar 

  95. Elbashir, S. M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 (2001).

    CAS  Google Scholar 

  96. Hammond, S. M., Bernstein, E., Beach, D. & Hannon, G. J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophilia cells. Nature 404, 293–296 (2000).

    CAS  Google Scholar 

  97. Zamore, P., Tuschl, T., Sharp, P. & Bartel, D. RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101, 25–33 (2000).

    CAS  Google Scholar 

  98. Oishi, M., Nagasaki, Y., Itaka, K., Nishiyama, N. & Kataoka, K. Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells. J. Am. Chem. Soc. 127, 1624–5 (2005).

    CAS  Google Scholar 

  99. Kim, S. H., Jeong, J. H., Cho, K. C., Kim, S. W. & Park, T. G. Target-specific gene silencing by siRNA plasmid DNA complexed with folate-modified poly(ethylenimine). J. Control. Rel. 104, 223–232 (2005).

    CAS  Google Scholar 

  100. Soutschek, J. et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173–178 (2004).

    CAS  Google Scholar 

  101. Chen, L. & Deem, M. W. Monte Carlo methods for small molecule high-throughput experimentation. J. Chem. Inf. Comput. Sci. 41, 950–957 (2001).

    CAS  Google Scholar 

  102. Maheshri, N. & Schaffer, D. V. Computational and experimental analysis of DNA shuffling. Proc. Natl Acad. Sci. USA 100, 3071–3076 (2003).

    CAS  Google Scholar 

  103. Brocchini, S., James, K., Tangpasuthadol, V. & Kohn, J. Structure-property correlations in a combinatorial library of degradable biomaterials. J. Biomed. Mater. Res. 42, 66–75 (1998).

    CAS  Google Scholar 

  104. Brocchini, S., James, K., Tangpasuthadol, V. & Kohn, J. A combinatorial approach for polymer design. J. Am. Chem. Soc. 119, 4553–4554 (1997).

    CAS  Google Scholar 

  105. Anderson, D. G., Putnam, D., Lavik, E. B., Mahmood, T. A. & Langer, R. Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction. Biomater. 26, 4892–4897 (2005).

    CAS  Google Scholar 

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Acknowledgements

The author thanks the many investigators who willingly shared their peer-reviewed and preliminary research results for inclusion in this review, and Anne Doody for her critical analysis of the manuscript. Financial support from the Whitaker Foundation, the Walter H. Coulter Foundation and the New York State Center for Advanced Technology is gratefully appreciated.

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Putnam, D. Polymers for gene delivery across length scales. Nature Mater 5, 439–451 (2006). https://doi.org/10.1038/nmat1645

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