Skip to main content
SpringerLink
Log in

Gene Delivery Using Polymer Therapeutics

  • Chapter
  • First Online:
Polymer Therapeutics I

Part of the book series: Advances in Polymer Science ((POLYMER,volume 192))

Abstract

The use of polymers as synthetic non-viral carriers for introducing nucleic acids into cells appears very appealing. Polymers can be generated in large quantities in chemically defined, non-antigenic and non-immunogenic form. A plethora of different chemical structures and polymer sizes may be applied to tailor-made polymers with optimized characteristics for the extracellular delivery of nucleic acid to the target tissue and the subsequent intracellular delivery into the target cells. For the purpose of nucleic acid transfer, polymers have been applied for incorporating nucleic acids into nanoparticles or microspheres. Alternatively, cationic polymers are applied as carriers for complexing gene vectors into polyplexes. Polyplexes form spontaneously upon mixing negatively charged nucleic acid with the polycationic polymer due to electrostatic interaction. This process can be controlled to result in the formation of particles with defined virus-like sizes which efficiently transfect cell cultures and also have shown encouraging gene transfer potential in in vivo administration. With first-generation polymeric carriers, gene therapeutic effects have been demonstrated in animals, although modest efficiencies and significant toxicity restrict broader therapeutic application. Key issues for future optimization of polyplexes include improved specificity for the target tissue, enhanced intracellular uptake, and reduced toxicity and immunogenicity. Novel cationic polymers have to be made more biocompatible by reducing their potential for unspecific adverse interactions with the host, and by designing them in a biodegradable form. “Smart” polymers and polymer conjugates are being developed that in a dynamic manner present virus-like delivery functions in the appropriate phase of the gene delivery process.

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

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

ASGP:

asialoglycoprotein

B-PEI:

branched PEI

BSA:

bovine serum albumine

CD:

cyclodextrin

EGF:

epidermal growth factor

HMW:

high molecular weight

i.v.:

intravenous

LLO:

listeriolysin-O

LMW:

low molecular weight

L-PEI:

linear PEI

Mel:

melittin

MW:

molecular weight

N/P ratio:

ratio of polymer nitrogens per DNA phosphate groups

n-PAE:

network polyamino ester

NVP:

N-vinyl-pyrrolidone

PAMAM:

dendrimer, polyamidoamine dendrimer

pDMAEMA:

poly(2-(dimethylamino) ethyl methacrylate)

pHPMA:

poly-N-2-hydroxypropyl-methacrylamide

PEG:

polyethylene glycol

PEI:

polyethylenimine

PHLP:

poly(d,l-lactide-co-4-hydroxyl-l-proline)

PLGA:

poly(lactide-co-glycolide)

pLL:

poly(l)lysine

PPE-PA:

poly(2-aminoethyl propylene phosphate)

PPI:

polypropylenimine

PVA:

poly(vinyl alcohol)

RPC:

reducible polycation

TNF:

tumor necrosis factor

References

  1. Duncan R (2003) The dawning era of polymer therapeutics. Nature Review 2:347–360

    CAS  Google Scholar 

  2. Berton M, Allemann E, Stein CA, Gurny R (1999) Eur J Pharm Sci 9:163

    CAS  Google Scholar 

  3. Truong L, Walsh SM, Schweibert E, Mao HQ, Guggino WB, August JT, Leong KW (1999) Arch Biochem Biophys 361:47

    Google Scholar 

  4. Mao HQ, Roy K, Troung L, Janes KA, Lin KY, Wang Y, August JT, Leong KW (2001) J Control Release 70:399

    CAS  Google Scholar 

  5. Cui Z, Mumper RJ (2002) Bioconjug Chem 13:1319

    Article  CAS  Google Scholar 

  6. Felgner PL, Barenholz Y, Behr JP, Cheng SH, Cullis P, Huang L, Jessee JA, Seymour L, Szoka F, Thierry AR, Wagner E, Wu G (1997) Hum Gene Ther 8:511

    CAS  Google Scholar 

  7. De Smedt SC, Demeester J, Hennink WE (2000) Pharm Res 17:113

    Google Scholar 

  8. Brown MD, Schatzlein AG, Uchegbu IF (2001) Int J Pharm 229:1

    Article  CAS  Google Scholar 

  9. Han S, Mahato RI, Sung YK, Kim SW (2000) Mol Ther 2:302

    Article  CAS  Google Scholar 

  10. Wagner E (2004) Pharm Res 21:8

    Article  CAS  Google Scholar 

  11. Vaheri A, Pagano JS (1965) Virology 27:434

    CAS  Google Scholar 

  12. Mislick KA, Baldeschwieler JD (1996) Proc Natl Acad Sci USA 93:12349

    Article  CAS  Google Scholar 

  13. Goncalves C, Pichon C, Guerin B, Midoux P (2002) J Gene Med 4:271

    Google Scholar 

  14. Goncalves C, Mennesson E, Fuchs R, Gorvel JP, Midoux P, Pichon C (2004) Mol Ther 10:373

    Article  CAS  Google Scholar 

  15. Kopatz I, Remy JS, Behr JP (2004) J Gene Med 6:769

    Article  CAS  Google Scholar 

  16. Ruponen M, Honkakoski P, Tammi M, Urtti A (2004) J Gene Med 6:405

    Article  CAS  Google Scholar 

  17. Wu GY, Wu CH (1987) J Biol Chem 262:4429

    CAS  Google Scholar 

  18. Wagner E, Zenke M, Cotten M, Beug H, Birnstiel ML (1990) Proc Natl Acad Sci USA 87:3410

    CAS  Google Scholar 

  19. Curiel DT, Agarwal S, Wagner E, Cotten M (1991) Proc Natl Acad Sci USA 88:8850

    CAS  Google Scholar 

  20. Lukacs GL, Haggie P, Seksek O, Lechardeur D, Freedman N, Verkman AS (2000) J iol Chem 275:1625

    CAS  Google Scholar 

  21. Ludtke JJ, Zhang G, Sebestyén MG, Wolff JA (1999) J Cell Sci 112:2033

    CAS  Google Scholar 

  22. Brunner S, Furtbauer E, Sauer T, Kursa M, Wagner E (2002) Mol Ther 5:80

    Article  CAS  Google Scholar 

  23. Schaffer DV, Fidelman NA, Dan N, Lauffenburger DA (2000) Biotechnol Bioeng 67:598

    Article  CAS  Google Scholar 

  24. Plank C, Tang MX, Wolfe AR, Szoka FC Jr (1999) Hum Gene Ther 10:319

    Article  CAS  Google Scholar 

  25. Parker AL, Oupicky D, Dash PR, Seymour LW (2002) Anal Biochem 302:75

    Article  CAS  Google Scholar 

  26. Reineke TM, Davis ME (2003) Bioconjug Chem 14:255

    CAS  Google Scholar 

  27. Reineke TM, Davis ME (2003) Bioconjug Chem 14:247

    CAS  Google Scholar 

  28. Chen QR, Zhang L, Luther PW, Mixson AJ (2002) Nucleic Acids Res 30:1338

    CAS  Google Scholar 

  29. Zauner W, Ogris M, Wagner E (1998) Advanced Drug Delivery Reviews 30(1–3):97

    Google Scholar 

  30. Wang J, Gao SJ, Zhang PC, Wang S, Mao HQ, Leong KW (2004) Gene Ther 11:1001

    CAS  Google Scholar 

  31. Wagner E, Cotten M, Foisner R, Birnstiel ML (1991) Proc Natl Acad Sci USA 88:4255

    CAS  Google Scholar 

  32. Wu GY, Wu CH (1988) J Biol Chem 262:14621

    Google Scholar 

  33. Chowdhury NR, Wu CH, Wu GY, Yerneni PC, Bommineni VR, Chowdhury JR (1993) J Biol Chem 268:11265

    CAS  Google Scholar 

  34. Wu GY, Wilson JM, Shalaby F, Grossman M, Shafritz DA, Wu CH (1991) J Biol Chem 266:14338

    CAS  Google Scholar 

  35. Wilson JM, Grossman M, Wu CH, Chowdhury NR, Wu GY, Chowdhury JR (1992) J Biol Chem 267:963

    CAS  Google Scholar 

  36. Perales JC, Ferkol T, Beegen H, Ratnoff OD, Hanson RW (1994) Proc Natl Acad Sci USA 91:4086

    CAS  Google Scholar 

  37. Ferkol T, Perales JC, Eckman E, Kaetzel CS, Hanson RW, Davis PB (1995) J Clin Invest 95:493

    CAS  Google Scholar 

  38. Ziady AG, Ferkol T, Dawson DV, Perlmutter DH, Davis PB (1999) J Biol Chem 274:4908

    Article  CAS  Google Scholar 

  39. Cotten M, Langle R, Kirlappos H, Wagner E, Mechtler K, Zenke M, Beug H, Birnstiel ML (1990) Proc Natl Acad Sci USA 87:4033

    CAS  Google Scholar 

  40. Zauner W, Blaas D, Kuechler E, Wagner E (1995) J Virol 69:1085

    CAS  Google Scholar 

  41. Hogset A, Prasmickaite L, Tjelle TE, Berg K (2000) Hum Gene Ther 11:869

    Article  CAS  Google Scholar 

  42. Prasmickaite L, Hogset A, Selbo PK, Engesaeter BO, Hellum M, Berg K (2002) Br J Cancer 86:652

    Article  CAS  Google Scholar 

  43. Prasmickaite L, Hogset A, Tjelle TE, Olsen VM, Berg K (2000) J Gene Med 2:477

    Article  CAS  Google Scholar 

  44. Prasmickaite L, Hogset A, Berg K (2001) Photochem Photobiol 73:388

    Article  CAS  Google Scholar 

  45. Prasmickaite L, Hogset A, Berg K (2002) Biochim Biophys Acta 1570:210

    CAS  Google Scholar 

  46. Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP (1995) Proc Natl Acad Sci USA 92:7297

    CAS  Google Scholar 

  47. Zou SM, Erbacher P, Remy JS, Behr JP (2000) J Gene Med 2:128

    Article  CAS  Google Scholar 

  48. Sonawane ND, Szoka FC Jr, Verkman AS (2003) J Biol Chem 278:44826

    Article  CAS  Google Scholar 

  49. Goula D, Becker N, Lemkine GF, Normandie P, Rodrigues J, Mantero S, Levi G, Demeneix BA (2000) Gene Ther 7:499

    CAS  Google Scholar 

  50. Chollet P, Favrot MC, Hurbin A, Coll JL (2002) J Gene Med 4:84

    Article  Google Scholar 

  51. Kircheis R, Schuller S, Brunner S, Heider K, Zauner W, Wagner E (1999) J Gene Med 1:111

    Article  CAS  Google Scholar 

  52. Rudolph C, Lausier J, Naundorf S, Muller RH, Rosenecker J (2000) J Gene Med 2:269

    Article  CAS  Google Scholar 

  53. Gautam A, Waldrep JC, Densmore CL, Koshkina N, Melton S, Roberts L, Gilbert B, Knight V (2002) Gene Ther 9:353

    CAS  Google Scholar 

  54. Ogris M, Steinlein P, Kursa M, Mechtler K, Kircheis R, Wagner E (1998) Gene Ther 5:1425

    CAS  Google Scholar 

  55. Wightman L, Kircheis R, Rossler V, Carotta S, Ruzicka R, Kursa M, Wagner E (2001) J Gene Med 3:362

    Article  CAS  Google Scholar 

  56. Boeckle S, von Gersdorff K, van der Piepen S, Culmsee C, Wagner E, Ogris M (2004) J Gene Med 6:1102

    Article  CAS  Google Scholar 

  57. Kloeckner J, Prasmickaite L, Hogset A, Berg K, Wagner E (2004) J Drug Targeting 12:205

    Article  CAS  Google Scholar 

  58. Haensler J, Szoka FC Jr (1993) Bioconjug Chem 4:372

    CAS  Google Scholar 

  59. Tang MX, Szoka FC (1997) Gene Ther 4:823

    CAS  Google Scholar 

  60. Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, Baker JR Jr (1996) Proc Natl Acad Sci USA 93:4897

    Article  CAS  Google Scholar 

  61. Kukowska-Latallo JF, Raczka E, Quintana A, Chen C, Rymaszewski M, Baker JR Jr (2000) Hum Gene Ther 11:1385

    Article  CAS  Google Scholar 

  62. Manunta M, Tan PH, Sagoo P, Kashefi K, George AJ (2004) Nucleic Acids Res 32:2730

    Article  CAS  Google Scholar 

  63. Mansouri S, Lavigne P, Corsi K, Benderdour M, Beaumont E, Fernandes JC (2004) Eur J Pharm Biopharm 57:1

    CAS  Google Scholar 

  64. Erbacher P, Zou S, Bettinger T, Steffan AM, Remy JS (1998) Pharm Res 15:1332

    Article  CAS  Google Scholar 

  65. Park IK, Kim TH, Park YH, Shin BA, Choi ES, Chowdhury EH, Akaike T, Cho CS (2001) J Control Release 76:349

    CAS  Google Scholar 

  66. Thanou M, Florea BI, Geldof M, Junginger HE, Borchard G (2002) Biomaterials 23:153

    Article  CAS  Google Scholar 

  67. Sato T, Ishii T, Okahata Y (2001) Biomaterials 22:2075

    Article  CAS  Google Scholar 

  68. Kim TH, Ihm JE, Choi YJ, Nah JW, Cho CS (2003) J Control Release 93:389

    CAS  Google Scholar 

  69. Cherng JY, van de WP, Talsma H, Crommelin DJ, Hennink WE (1996) Pharm Res 13:1038

    Google Scholar 

  70. van de WP, Cherng JY, Talsma H, Crommelin DJ, Hennink WE (1998) J Control Release 53:145

    Google Scholar 

  71. van de WP, Schuurmans-Nieuwenbroek NM, Hennink WE, Storm G (1999) J Gene Med 1:156

    Google Scholar 

  72. Verbaan FJ, Oussoren C, van Dam IM, Takakura Y, Hashida M, Crommelin DJ, Hennink WE, Storm G (2001) Int J Pharm 214:99

    Article  CAS  Google Scholar 

  73. Funhoff AM, van Nostrum CF, Koning GA, Schuurmans-Nieuwenbroek NM, Crommelin DJ, Hennink WE (2004) Biomacromolecules 5:32

    Article  CAS  Google Scholar 

  74. Hwang SJ, Bellocq NC, Davis ME (2001) Bioconjug Chem 12:280

    Article  CAS  Google Scholar 

  75. Bellocq NC, Pun SH, Jensen GS, Davis ME (2003) Bioconjug Chem 14:1122

    Article  CAS  Google Scholar 

  76. Cryan SA, Holohan A, Donohue R, Darcy R, O'Driscoll CM (2004) Eur J Pharm Sci 21:625

    CAS  Google Scholar 

  77. Arima H, Kihara F, Hirayama F, Uekama K (2001) Bioconjug Chem 12:476

    Article  CAS  Google Scholar 

  78. Kihara F, Arima H, Tsutsumi T, Hirayama F, Uekama K (2003) Bioconjug Chem 14:342

    Article  CAS  Google Scholar 

  79. Pun SH, Bellocq NC, Liu A, Jensen G, Machemer T, Quijano E, Schluep T, Wen S, Engler H, Heidel J, Davis ME (2004) Bioconjug Chem 15:831

    Article  CAS  Google Scholar 

  80. Kabanov AV, Batrakova EV, Alakhov VY (2002) J Control Release 82:189

    CAS  Google Scholar 

  81. Lemieux P, Guerin N, Paradis G, Proulx R, Chistyakova L, Kabanov A, Alakhov V (2000) Gene Ther 7:986

    CAS  Google Scholar 

  82. Nguyen HK, Lemieux P, Vinogradov SV, Gebhart CL, Guérin N, Paradis G, Bronich TK, Alakhov VY, Kabanov AV (2000) Gene Ther 7:126

    CAS  Google Scholar 

  83. Belenkov AI, Alakhov VY, Kabanov AV, Vinogradov SV, Panasci LC, Monia BP, Chow TY (2004) Gene Ther 22:1665

    Google Scholar 

  84. Li Z, Huang L (2004) J Control Release 98:437

    CAS  Google Scholar 

  85. Bello Roufai M, Midoux P (2001) Bioconjug Chem 12:92

    CAS  Google Scholar 

  86. Putnam D, Gentry CA, Pack DW, Langer R (2001) Proc Natl Acad Sci USA 98:1200

    Article  CAS  Google Scholar 

  87. Kichler A (2004) J Gene Med 6:S3

    Article  CAS  Google Scholar 

  88. Ogris M, Brunner S, Schueller S, Kircheis R, Wagner E (1999) Gene Ther 6:595

    CAS  Google Scholar 

  89. Petersen H, Fechner PM, Martin AL, Kunath K, Stolnik S, Roberts CJ, Fischer D, Davies MC, Kissel T (2002) Bioconjug Chem 13:845

    CAS  Google Scholar 

  90. Kichler A, Chillon M, Leborgne C, Danos O, Frisch B (2002) J Control Release 81:379

    CAS  Google Scholar 

  91. Kursa M, Walker GF, Roessler V, Ogris M, Roedl W, Kircheis R, Wagner E (2003) Bioconjug Chem 14:222

    Article  CAS  Google Scholar 

  92. Ogris M, Walker G, Blessing T, Kircheis R, Wolschek M, Wagner E (2003) J Control Release 91:173

    CAS  Google Scholar 

  93. Hong JW, Park JH, Huh KM, Chung H, Kwon IC, Jeong SY (2004) J Control Release 99:167

    CAS  Google Scholar 

  94. Tseng WC, Jong CM (2003) Biomacromolecules 4:1277

    Article  CAS  Google Scholar 

  95. Brissault B, Kichler A, Guis C, Leborgne C, Danos O, Cheradame H (2003) Bioconjug Chem 14:581

    Article  CAS  Google Scholar 

  96. Jeong JH, Song SH, Lim DW, Lee H, Park TG (2001) J Control Release 73:391

    CAS  Google Scholar 

  97. Thomas M, Klibanov AM (2002) Proc Natl Acad Sci USA 99:14640

    CAS  Google Scholar 

  98. Fischer D, von Harpe A, Kunath K, Petersen H, Li Y, Kissel T (2002) Bioconjug Chem 13:1124

    Article  CAS  Google Scholar 

  99. Brownlie A, Uchegbu IF, Schatzlein AG (2004) Int J Pharm 274:41

    Article  CAS  Google Scholar 

  100. Forrest ML, Meister GE, Koerber JT, Pack DW (2004) Pharm Res 21:365

    Article  CAS  Google Scholar 

  101. Wang DA, Narang AS, Kotb M, Gaber AO, Miller DD, Kim SW, Mahato RI (2002) Biomacromolecules 3:1197

    CAS  Google Scholar 

  102. Furgeson DY, Chan WS, Yockman JW, Kim SW (2003) Bioconjug Chem 14:840

    Article  CAS  Google Scholar 

  103. Sochanik A, Cichon T, Makselon M, Strozyk M, Smolarczyk R, Jazowiecka-Rakus J, Szala S (2004) Acta Biochim Pol 51:693

    CAS  Google Scholar 

  104. Choi JS, Nam K, Park JY, Kim JB, Lee JK, Park JS (2004) J Control Release 99:445

    CAS  Google Scholar 

  105. Ohsaki M, Okuda T, Wada A, Hirayama T, Niidome T, Aoyagi H (2002) Bioconjug Chem 13:510

    Article  CAS  Google Scholar 

  106. Okuda T, Sugiyama A, Niidome T, Aoyagi H (2004) Biomaterials 25:537

    Article  CAS  Google Scholar 

  107. Kawano T, Okuda T, Aoyagi H, Niidome T (2004) J Control Release 99:329

    CAS  Google Scholar 

  108. Zinselmeyer BH, Mackay SP, Schatzlein AG, Uchegbu IF (2002) Pharm Res 19:960

    Article  CAS  Google Scholar 

  109. Uchegbu IF, Dufes C, Elouzi A, Schatzlein AG (2004) Proceed 12th Int Pharm Techn Symp 2004:11

    Google Scholar 

  110. Banerjee P, Reichardt W, Weissleder R, Bogdanov A Jr (2004) Bioconjug Chem 15:960

    Article  CAS  Google Scholar 

  111. Kramer M, Stumbe JF, Grimm G, Kaufmann B, Kruger U, Weber M, Haag R (2004) Chembiochem 5:1081

    Google Scholar 

  112. Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T (1999) Pharm Res 16:1273

    Article  CAS  Google Scholar 

  113. Ahn CH, Chae SY, Bae YH, Kim SW (2004) J Control Release 97:567

    CAS  Google Scholar 

  114. Lim YB, Han SO, Kong HU, Lee Y, Park JS, Jeong B, Kim SW (2000) Pharm Res 17:811

    Article  CAS  Google Scholar 

  115. Lim Y, Choi YH, Park J (1999) J Am Chem Soc 121:5633

    Article  CAS  Google Scholar 

  116. Anderson DG, Lynn DM, Langer R (2003) Angew Chem Int Ed Engl 42:3153

    Article  CAS  Google Scholar 

  117. Akinc A, Anderson DG, Lynn DM, Langer R (2003) Bioconjug Chem 14:979

    Article  CAS  Google Scholar 

  118. Lim YB, Kim SM, Suh H, Park JS (2002) Bioconjug Chem 13:952

    CAS  Google Scholar 

  119. Oster CG, Wittmar M, Unger F, Barbu-Tudoran L, Schaper AK, Kissel T (2004) Pharm Res 21:927

    Article  CAS  Google Scholar 

  120. Funhoff AM, van Nostrum CF, Janssen AP, Fens MH, Crommelin DJ, Hennink WE (2004) Pharm Res 21:170

    Article  CAS  Google Scholar 

  121. Mechtler K, Wagner E (1997) New J Chem 21:105

    CAS  Google Scholar 

  122. Ahn CH, Chae SY, Bae YH, Kim SW (2002) J Control Release 80:273

    CAS  Google Scholar 

  123. Petersen H, Merdan T, Kunath K, Fischer D, Kissel T (2002) Bioconjug Chem 13:812

    CAS  Google Scholar 

  124. Forrest ML, Koerber JT, Pack DW (2003) Bioconjug Chem 14:934

    Article  CAS  Google Scholar 

  125. Zhao Z, Wang J, Mao HQ, Leong KW (2003) Adv Drug Deliv Rev 55:483

    Article  CAS  Google Scholar 

  126. Wang J, Mao HQ, Leong KW (2001) J Am Chem Soc 123:9480

    CAS  Google Scholar 

  127. Wang J, Zhang PC, Mao HQ, Leong KW (2002) Gene Ther 9:1254

    CAS  Google Scholar 

  128. Wang J, Zhang PC, Lu HF, Ma N, Wang S, Mao HQ, Leong KW (2002) J Control Release 83:157

    CAS  Google Scholar 

  129. Asokan A, Cho M (2002) J Pharm Sci 91:903

    Article  CAS  Google Scholar 

  130. Wang C, Ge Q, Ting D, Nguyen D, Shen HR, Chen J, Eisen HN, Heller J, Langer R, Putnam D (2004) Nat Mater 3:190

    CAS  Google Scholar 

  131. Murthy N, Campbell J, Fausto N, Hoffman AS, Stayton PS (2003) J Control Release 89:365

    CAS  Google Scholar 

  132. Lackey CA, Press OW, Hoffman AS, Stayton PS (2002) Bioconjug Chem 13:996

    Article  CAS  Google Scholar 

  133. Walker GF, Fella C, Pelisek J, Fahrmeir J, Boeckle S, Ogris M, Wagner E (2005) Mol Ther 11:418

    Article  CAS  Google Scholar 

  134. Saito G, Swanson JA, Lee KD (2003) Adv Drug Deliv Rev 55:199

    Article  CAS  Google Scholar 

  135. Kakizawa Y, Harada A, Kataoka K (1999) J Am Chem Soc 121:11247

    Article  CAS  Google Scholar 

  136. Kakizawa Y, Harada A, Kataoka K (2001) Biomacromolecules 2:491

    Article  CAS  Google Scholar 

  137. Collins DS, Unanue ER, Harding CV (1991) J Immunol 147:4054

    CAS  Google Scholar 

  138. McKenzie DL, Smiley E, Kwok KY, Rice KG (2000) Bioconjug Chem 11:901

    Article  CAS  Google Scholar 

  139. McKenzie DL, Kwok KY, Rice KG (2000) J Biol Chem 275:9970

    CAS  Google Scholar 

  140. Park Y, Kwok KY, Boukarim C, Rice KG (2002) Bioconjug Chem 13:232

    Article  CAS  Google Scholar 

  141. Kwok KY, Park Y, Yang Y, McKenzie DL, Liu Y, Rice KG (2003) J Pharm Sci 92:1174

    Article  CAS  Google Scholar 

  142. Oupicky D, Carlisle RC, Seymour LW (2001) Gene Ther 8:713

    CAS  Google Scholar 

  143. Oupicky D, Parker AL, Seymour LW (2002) J Am Chem Soc 124:8

    Article  CAS  Google Scholar 

  144. Read ML, Bremner KH, Oupicky D, Green NK, Searle PF, Seymour LW (2003) J Gene Med 5:232

    Article  CAS  Google Scholar 

  145. Trubetskoy VS, Loomis A, Slattum PM, Hagstrom JE, Budker VG, Wolff JA (1999) Bioconjug Chem 10:624

    Article  CAS  Google Scholar 

  146. Miyata K, Kakizawa Y, Nishiyama N, Harada A, Yamasaki Y, Koyama H, Kataoka K (2004) J Am Chem Soc 126:2355

    Article  CAS  Google Scholar 

  147. Pichon C, LeCam E, Guerin B, Coulaud D, Delain E, Midoux P (2002) Bioconjug Chem 13:76

    Article  CAS  Google Scholar 

  148. Gosselin MA, Guo W, Lee RJ (2001) Bioconjug Chem 12:989

    Article  CAS  Google Scholar 

  149. Guo W, Lee RJ (1999) AAPS Pharmsci 1:Article 19

    Google Scholar 

  150. Mislick KA, Baldeschwieler JD, Kayyem JF, Meade TJ (1995) Bioconjug Chem 6:512

    Article  CAS  Google Scholar 

  151. Plank C, Zatloukal K, Cotten M, Mechtler K, Wagner E (1992) Bioconjug Chem 3:533

    Article  CAS  Google Scholar 

  152. Nishikawa M, Yamauchi M, Morimoto K, Ishida E, Takakura Y, Hashida M (2000) Gene Ther 7:548

    CAS  Google Scholar 

  153. Kim TG, Kang SY, Kang JH, Cho MY, Kim JI, Kim SH, Kim JS (2004) Bioconjug Chem 15:326

    CAS  Google Scholar 

  154. Wolschek MF, Thallinger C, Kursa M, Rossler V, Allen M, Lichtenberger C, Kircheis R, Lucas T, Willheim M, Reinisch W, Gangl A, Wagner E, Jansen B (2002) Hepatology 36:1106

    Article  CAS  Google Scholar 

  155. Sosnowski BA, Gonzalez AM, Chandler LA, Buechler YJ, Pierce GF, Baird A (1996) J Biol Chem 271:33647

    CAS  Google Scholar 

  156. Chiu SJ, Ueno NT, Lee RJ (2004) J Control Release 97:357

    CAS  Google Scholar 

  157. Buschle M, Cotten M, Kirlappos H, Mechtler K, Schaffner G, Zauner W, Birnstiel ML, Wagner E (1995) Hum Gene Ther 6:753

    CAS  Google Scholar 

  158. Merdan T, Callahan J, Petersen H, Kunath K, Bakowsky U, Kopeckova P, Kissel T, Kopecek J (2003) Bioconjug Chem 14:989

    Article  CAS  Google Scholar 

  159. Li S, Tan Y, Viroonchatapan E, Pitt BR, Huang L (2000) Am J Physiol Lung Cell Mol Physiol 278:504

    Google Scholar 

  160. Schatzlein AG (2003) J Biomed Biotechnol 2003:149

    Google Scholar 

  161. Wagner E, Culmsee C, Boeckle S (2005) Targeting of Polyplexes: Towards Synthetic Virus Vector Systems. In: Huang L, Hung MC, Wagner E (eds) Nonviral Vectors for Gene Therapy, Second Edition (Advances in Genetics, vol 53)

    Google Scholar 

  162. Kircheis R, Wightman L, Schreiber A, Robitza B, Rossler V, Kursa M, Wagner E (2001) Gene Ther 8:28

    CAS  Google Scholar 

  163. Plank C, Mechtler K, Szoka FJ, Wagner E (1996) Hum Gene Ther 7:1437

    CAS  Google Scholar 

  164. Verbaan FJ, Oussoren C, Snel CJ, Crommelin DJ, Hennink WE, Storm G (2004) J Gene Med 6:64

    Article  CAS  Google Scholar 

  165. Fisher KD, Ulbrich K, Subr V, Ward CM, Mautner V, Blakey D, Seymour LW (2000) Gene Ther 7:1337

    CAS  Google Scholar 

  166. Kircheis R, Ostermann E, Wolschek MF, Lichtenberger C, Magin-Lachmann C, Wightman L, Kursa M, Wagner E (2002) Cancer Gene Ther 9:673

    CAS  Google Scholar 

  167. Wagner E, Zatloukal K, Cotten M, Kirlappos H, Mechtler K, Curiel DT, Birnstiel ML (1992) Proc Natl Acad Sci USA 89:6099

    CAS  Google Scholar 

  168. Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Biochem J 377:159

    Article  CAS  Google Scholar 

  169. Plank C, Zauner W, Wagner E (1998) Adv Drug Deliv Rev 34:21

    Article  CAS  Google Scholar 

  170. Boeckle S, Wagner E, Ogris M (2002) Transmembrane Targeting of DNA with Membrane Active Peptides. In: Muzykantov VR, Torchilin VP (eds) Biomedical Aspects of Drug Targeting. Kluwer Academic Publishers, Boston=Dordrecht=London Chap 23, p 441

    Google Scholar 

  171. Cristiano RJ, Smith LC, Kay MA, Brinkley BR, Woo SL (1993) Proc Natl Acad Sci USA 90:11548

    CAS  Google Scholar 

  172. Wu GY, Zhan P, Sze LL, Rosenberg AR, Wu CH (1994) J Biol Chem 269:11542

    CAS  Google Scholar 

  173. Fisher KJ, Wilson JM (1994) Biochem J 299:49

    CAS  Google Scholar 

  174. Fender P, Ruigrok RW, Gout E, Buffet S, Chroboczek J (1997) Nat Biotechnol 15:52

    Article  CAS  Google Scholar 

  175. Gottschalk S, Tweten RK, Smith LC, Woo SL (1995) Gene Ther 2:498

    CAS  Google Scholar 

  176. Fisher KJ, Wilson JM (1997) Biochem J 321:49

    CAS  Google Scholar 

  177. Gottschalk S, Sparrow JT, Hauer J, Mims MP, Leland FE, Woo SL, Smith LC (1996) Gene Ther 3:48

    CAS  Google Scholar 

  178. Ogris M, Carlisle RC, Bettinger T, Seymour LW (2001) J Biol Chem 276:47550

    Article  CAS  Google Scholar 

  179. Kichler A, Mechtler K, Behr JP, Wagner E (1997) Bioconjug Chem 8:213

    Article  CAS  Google Scholar 

  180. Bettinger T, Carlisle RC, Read ML, Ogris M, Seymour LW (2001) Nucleic Acids Res 29:3882

    Article  CAS  Google Scholar 

  181. Boeckle S, Ogris M, Wagner E (2005) J Gene Med 7:1335

    Article  CAS  Google Scholar 

  182. Saito G, Amidon GL, Lee KD (2003) Gene Ther 10:72

    CAS  Google Scholar 

  183. Berg K, Selbo PK, Prasmickaite L, Tjelle TE, Sandvig K, Moan J, Gaudernack G, Fodstad O, Kjolsrud S, Anholt H, Rodal GH, Rodal SK, Hogset A (1999) Cancer Res 59:1180

    CAS  Google Scholar 

  184. Zabner J, Fasbender AJ, Moninger T, Poellinger KA, Welsh MJ (1995) J Biol Chem 270:18997

    CAS  Google Scholar 

  185. Brunner S, Sauer T, Carotta S, Cotten M, Saltik M, Wagner E (2000) Gene Ther 7:401

    CAS  Google Scholar 

  186. Sebestyen MG, Ludtke JJ, Bassik MC, Zhang G, Budker V, Lukhtanov EA, Hagstrom JE, Wolff JA (1998) Nat Biotechnol 16:80

    CAS  Google Scholar 

  187. Zuber G, Dauty E, Nothisen M, Belguise P, Behr JP (2001) Adv Drug Deliv Rev 52:245

    Article  CAS  Google Scholar 

  188. Rozema DB, Ekena K, Lewis DL, Loomis AG, Wolff JA (2003) Bioconjug Chem 14:51

    Article  CAS  Google Scholar 

  189. Carlisle RC, Etrych T, Briggs SS, Preece JA, Ulbrich K, Seymour LW (2004) J Gene Med 6:337

    Article  CAS  Google Scholar 

  190. Blessing QT, Remy JS, Behr JP (1998) Proc Natl Acad Sci USA 95:1427

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The contributions to our research by Carolin Fella, Greg Walker, Julia Fahrmeir, Katharina von Gersdorff, Manfred Ogris, Sabine Boeckle, Silke van der Piepen and Wolfgang Rödl are greatly appreciated. It has been an exceptional pleasure to work within such a fantastic team. We are very grateful to Dr. Greg Walker for the careful review of the manuscript. Many thanks to Olga Brück for skilful assistance in preparing the manuscript.

Author information

Authors and Affiliations

  1. Pharmaceutical Biotechnology, Department of Pharmacy, Butenandtstrasse 5--13, 81377, Munich, Germany

    Ernst Wagner & Julia Kloeckner

Authors
  1. Ernst Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julia Kloeckner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ernst Wagner .

Editor information

Ronit Satchi-Fainaro Ruth Duncan

Rights and permissions

Reprints and permissions

About this chapter

Cite this chapter

Wagner, E., Kloeckner, J. Gene Delivery Using Polymer Therapeutics. In: Satchi-Fainaro, R., Duncan, R. (eds) Polymer Therapeutics I. Advances in Polymer Science, vol 192. Springer, Berlin, Heidelberg. https://doi.org/10.1007/12_023

Download citation

Publish with us

Policies and ethics

Search

Navigation