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Drug Delivery for the Retina and Posterior Segment Disease pp 131–149Cite as

Nonviral Delivery Systems for Gene Therapy for Retina and Posterior Segment Disease

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Abstract

Gene therapy is a hopeful strategy for the treatment of retinal disorders with no effective treatment. Gene replacement therapy is the most widely used strategy to modulate the gene expression in clinical research of inherited or acquired ocular diseases. Viral vectors are at the forefront of translational gene therapy mainly due to their high efficacy; nevertheless, concerns regarding safety have fostered the progress of nonviral therapy. Nonviral systems are non-immunogenic and avoid the risk of insertional mutagenesis. Moreover, they can be easily produced at large scale and have the potential to deliver larger genetic payloads. However, vector engineering to attain tissue-selective targeting and/or regulate the extent of gene expression is a challenging issue of nonviral gene therapy. Subretinal or intravitreal injections are the best option for the success of gene delivery to the posterior segment of the eye, regardless of the type of vector used. Preclinical studies with nonviral vectors have shown encouraging results for the treatment of macular degeneration and some inherited retinal disorders such as X-linked retinoschisis, Stargardt disease, retinitis pigmentosa, and Leber congenital amaurosis. These recent advances point to nonviral gene therapy as a feasible therapeutic tool for retinal disorders.

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References

  1. Abul-Hassan K, et al. Optimization of non-viral gene transfer to human primary retinal pigment epithelial cells. Curr Eye Res. 2000;20:361–6.

    Article  CAS  PubMed  Google Scholar 

  2. Aied A, et al. Polymer gene delivery: overcoming the obstacles. Drug Discov Today. 2013;18:1090–8.

    Article  CAS  PubMed  Google Scholar 

  3. Al-Saikhan FI. The gene therapy revolution in ophthalmology. Saudi J Ophthalmol. 2013;27:107–11.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Allikmets R, et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997;15:236–46.

    Article  CAS  PubMed  Google Scholar 

  5. Apaolaza PS, et al. A novel gene therapy vector based on hyaluronic acid and solid lipid nanoparticles for ocular diseases. Int J Pharm. 2014;465:413–26.

    Article  CAS  PubMed  Google Scholar 

  6. Apaolaza PS, et al. Solid lipid nanoparticle-based vectors intended for the treatment of X-linked juvenile retinoschisis by gene therapy: in vivo approaches in Rs1h-deficient mouse model. J Control Release. 2015;217:273–83.

    Article  CAS  PubMed  Google Scholar 

  7. Apaolaza PS, et al. Structural recovery of the retina in a retinoschisin-deficient mouse after gene replacement therapy by solid lipid nanoparticles. Biomaterials. 2016;90:40–9.

    Article  CAS  PubMed  Google Scholar 

  8. Arnedo A, et al. Albumin nanoparticles improved the stability, nuclear accumulation and anticytomegaloviral activity of a phosphodiester oligonucleotide. J Control Release. 2004;94:217–27.

    Article  CAS  PubMed  Google Scholar 

  9. Bainbridge JW, et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med. 2008;358:2231–9.

    Article  CAS  PubMed  Google Scholar 

  10. Banin E, et al. Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel. Hum Gene Ther. 2010;21:749–1757.

    Article  CAS  Google Scholar 

  11. Battaglia L, et al. Application of lipid nanoparticles to ocular drug delivery. Expert Opin Drug Deliv. 2016;13:1743–57.

    Article  CAS  PubMed  Google Scholar 

  12. Bejjani RA, et al. Nanoparticles for gene delivery to retinal pigment epithelial cells. Mol Vis. 2005;11:124–32.

    CAS  PubMed  Google Scholar 

  13. Berger W, et al. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res. 2010;29:335–75.

    Article  CAS  PubMed  Google Scholar 

  14. Binley K, et al. Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease. Invest Ophthalmol Vis Sci. 2013;54:4061–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bitoque DB, et al. Efficiency of RAFT-synthesized PDMAEMA in gene transfer to the retina. J Tissue Eng Regen Med. 2017;11:265–75.

    Article  CAS  PubMed  Google Scholar 

  16. Bloquel C, et al. Potential ocular therapeutic avenues. Adv Drug Deliv Rev. 2006;58:1224–42.

    Article  CAS  PubMed  Google Scholar 

  17. Breunig M, et al. Gene delivery with low molecular weight linear polyethylenimines. J Gene Med. 2005;7:1287–98.

    Article  CAS  PubMed  Google Scholar 

  18. Bush RA, et al. Convergence of human genetics and animal studies: gene therapy for X-linked retinoschisis. Cold Spring Harb Perspect Med. 2015;5:a017368.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Bush RA, et al. Preclinical dose-escalation study of intravitreal AAV-RS1 gene therapy in a mouse model of X-linked Retinoschisis: dose-dependent expression and improved retinal structure and function. Hum Gene Ther. 2016;27:376–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cai X, et al. Nanoparticle applications in ocular gene therapy. Vis Res. 2008;48:319–24.

    Article  CAS  PubMed  Google Scholar 

  21. Cai X, et al. Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa. FASEB J. 2010;24:1178–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Campochiaro PA, et al. Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age-related macular degeneration: results of a phase I clinical trial. Hum Gene Ther. 2006;17:167–76.

    Article  CAS  PubMed  Google Scholar 

  23. Carrasquillo KG, et al. Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic)acid microspheres. Invest Ophthalmol Vis Sci. 2003;44:290–9.

    Article  PubMed  Google Scholar 

  24. Chalberg TW, et al. phiC31 integrase confers genomic integration and long-term transgene expression in rat retina. Invest Ophthalmol Vis Sci. 2005;46:2140–6.

    Article  PubMed  Google Scholar 

  25. Chen CW, et al. Efficient downregulation of VEGF in retinal pigment epithelial cells by integrin ligand-labeled liposome-mediated siRNA delivery. Int J Nanomedicine. 2013;8:2613–27.

    PubMed  PubMed Central  Google Scholar 

  26. Cheung LK, Eaton A. Age-related macular degeneration. Pharmacotherapy. 2013;33:838–55.

    Article  CAS  PubMed  Google Scholar 

  27. Cideciyan AV, et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci U S A. 2008;105:15112–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Clinical-Trials.gov. Phase I/IIa study of SAR422459 in patients with Stargardt’s macular degeneration. StarGen, Clinical-Trialsgov number, NCT01367444. https://clinicaltrials.gov/ct2/show/NCT01367444. Last query: 26 June 2017.

  29. Cohen RN, et al. Quantification of plasmid DNA copies in the nucleus after lipoplex and polyplex transfection. J Control Release. 2009;135:166–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Conley SM, Naash MI. Nanoparticles for retinal gene therapy. Prog Retin Eye Res. 2010;29:376–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Connell G, et al. Photoreceptor peripherin is the normal product of the gene responsible for retinal degenera-tion in the rds mouse. Proc Natl Acad Sci U S A. 1991;88:723–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cox DB, et al. Therapeutic genome editing: prospects and challenges. Nat Med. 2015;21:121–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cremers FP, et al. Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in Stargardts disease ABCR. Hum Mol Gen. 1998;7:355–62.

    Article  CAS  PubMed  Google Scholar 

  34. D’Cruz PM, et al. Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet. 2000;9:645–51.

    Article  PubMed  Google Scholar 

  35. de la Fuente M, et al. Novel hyaluronic acid-chitosan nanoparticles for ocular gene therapy. Invest Ophthalmol Vis Sci. 2008;49:2016–24.

    Article  PubMed  Google Scholar 

  36. del Pozo-Rodríguez A, et al. Solid lipid nanoparticles for retinal gene therapy: transfection and intracellular trafficking in RPE cells. Int J Pharm. 2008;360:177–83.

    Article  PubMed  CAS  Google Scholar 

  37. del Pozo-Rodríguez A, et al. A proline-rich peptide improves cell transfection of solid lipid nanoparticle-based non-viral vectors. J Control Release. 2009;133:52–9.

    Article  PubMed  CAS  Google Scholar 

  38. del Pozo-Rodríguez A, et al. Lipid nanoparticles as drug/gene delivery systems to the retina. J Ocul Pharmacol Ther. 2013;29:173–88.

    Article  PubMed  CAS  Google Scholar 

  39. del Pozo-Rodríguez A, et al. Applications of lipid nanoparticles in gene therapy. Eur J Pharm Biopharm. 2016;109:184–93.

    Article  PubMed  CAS  Google Scholar 

  40. Delgado D, et al. Understanding the mechanism of protamine in solid lipid nanoparticle-based lipofection: the importance of the entry pathway. Eur J Pharm Biopharm. 2011;79:495–502.

    Article  CAS  PubMed  Google Scholar 

  41. Delgado D, et al. Dextran-protamine-solid lipid nanoparticles as a non-viral vector for gene therapy: in vitro characterization and in vivo transfection after intravenous administration to mice. Int J Pharm. 2012a;425:35–43.

    Article  CAS  PubMed  Google Scholar 

  42. Delgado D, et al. Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis. Hum Gene Ther. 2012b;23:345–55.

    Article  CAS  PubMed  Google Scholar 

  43. Delgado D, et al. New gene delivery system based on oligochitosan and solid lipid nanoparticles: ‘in vitro’ and ‘in vivo’ evaluation. Eur J Pharm Sci. 2013;50:484–91.

    Article  CAS  PubMed  Google Scholar 

  44. European Medicines Agency. Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products. Draft. EMA/CAT/80183/2014, 2015.

    Google Scholar 

  45. Feng L, et al. Ocular delivery of pRNA nanoparticles: distribution and clearance after subconjunctival injection. Pharm Res. 2014;31:1046–58.

    Article  CAS  PubMed  Google Scholar 

  46. Feret A, et al. Macular degeneration: types, causes, and possible interventions. Geriatr Nurs. 2007;28:387–92.

    Article  PubMed  Google Scholar 

  47. Foged C. siRNA delivery with lipid-based systems: promises and pitfalls. Curr Top Med Chem. 2012;12:97–107.

    Article  CAS  PubMed  Google Scholar 

  48. Fritsche LG, et al. Seven new loci associated with age-related macular degeneration. Nat Genet. 2013;45:433–9.

    Article  CAS  PubMed  Google Scholar 

  49. Gan L, et al. Hyaluronan-modified core-shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection. Biomaterials. 2013;34:5978–87.

    Article  CAS  PubMed  Google Scholar 

  50. Gene Therapy Clin Trials Worldwide. Provided by the Journal of GeneMedicine. Jon Wiley and Sons Ltd., 2017. http://www.abedia.com/wiley/indications.php. Updated Apr 2017; last query: 26 June 2017.

  51. Ghazi NG, et al. Treatment of retinitis pigmentosa due to MERTK mutations by ocular sub-retinal injection of adeno-associated virus gene vector: results of a phase I trial. Hum Genet. 2016;135:327–43.

    Article  CAS  PubMed  Google Scholar 

  52. Gomes dos Santos AL, et al. Oligonucleotide-polyethylenimine complexes targeting retinal cells: structural analysis and application to anti-TGFbeta-2 therapy. Pharm Res. 2006;23:770–81.

    Article  CAS  PubMed  Google Scholar 

  53. Hafler BP. Clinical progress in inherited retinal degenerations: gene therapy clinical trials and advances in genetic sequencing. Retina. 2017;37:417–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hamel C. Retinitis pigmentosa. Orphanet J Rare Dis. 2006;1:40.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Han Z, et al. DNA nanoparticle-mediated ABCA4 delivery rescues Stargardt dystrophy in mice. J Clin Invest. 2012;122:3221–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Janssen A, et al. Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin deficient mouse. Mol Ther. 2008;16:1010–7.

    Article  CAS  PubMed  Google Scholar 

  57. Johnen S, et al. Sleeping Beauty transposon-mediated transfection of retinal and iris pigment epithelial cells. Invest Ophthalmol Vis Sci. 2012;53:4787–96.

    Article  CAS  PubMed  Google Scholar 

  58. Hudecek M, et al. Going non-viral: the sleeping beauty transposon system breaks on through to the clinical side. Crit Rev Biochem Mol Biol. 2017;52:355–80.

    Article  CAS  PubMed  Google Scholar 

  59. Horbinski C, et al. Polyethyleneimine-mediated transfection of cultured postmitotic neurons from rat sympathetic ganglia and adult human retina. BMC Neurosci. 2001;2:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kaur IP, Kakkar S. Nanotherapy for posterior eye diseases. J Control Release. 2014;193:100–12.

    Article  CAS  PubMed  Google Scholar 

  61. Kay MA, et al. A robust system for production of minicircle DNA vectors. Nature Biotech. 2010;28:1287–9.

    Article  CAS  Google Scholar 

  62. Koirala A, et al. A review of therapeutic prospects of non-viral gene therapy in the retinal pigment epithelium. Biomaterials. 2013a;34:7158–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Koirala A, et al. S/MAR-containing DNA nanoparticles promote persistent RPE gene expression and improvement in RPE65-associated LCA. Hum Mol Genet. 2013b;22:1632–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Koirala A, et al. Episomal maintenance of S/MAR-containing non-viral vectors for RPE-based diseases. Adv Exp Med Biol. 2014;801:703–9.

    Article  PubMed  Google Scholar 

  65. Kurosaki T, et al. Ocular gene delivery systems using ternary complexes of plasmid DNA, polyethylenimine, and anionic polymers. Biol Pharm Bull. 2013;36:96–101.

    Article  CAS  PubMed  Google Scholar 

  66. Ladas ID, et al. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab: our experience after 2,000 injections. Retina. 2009;29:313–8.

    Article  PubMed  Google Scholar 

  67. Lhériteau E, et al. Successful gene therapy in the RPGRIP1-deficient dog: a large model of cone-rod dystrophy. Mol Ther. 2014;22:265–77.

    Article  PubMed  CAS  Google Scholar 

  68. Maguire AM, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358:2240–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mannermaa E, et al. Long-lasting secretion of transgene product from differentiated and filter-grown retinal pigment epithelial cells after nonviral gene transfer. Curr Eye Res. 2005;30:345–53.

    Article  CAS  PubMed  Google Scholar 

  70. Männistö M, et al. Structure-activity relationships of poly(L-lysines): effects of pegylation and molecular shape on physicochemical and biological properties in gene delivery. J Control Release. 2002;83:169–82.

    Article  PubMed  Google Scholar 

  71. Marano RJ, et al. Inhibition of in vitro VEGF expression and choroidal neovascularization by synthetic dendrimer peptide mediated delivery of a sense oligonucleotide. Exp Eye Res. 2004;79:525–35.

    Article  CAS  PubMed  Google Scholar 

  72. Martinez-Mir A, et al. Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease ABCR. Nat Genet. 1998;18:11–2.

    Article  CAS  PubMed  Google Scholar 

  73. Mashal M, et al. Retinal gene delivery enhancement by lycopene incorporation into cationic niosomes based on DOTMA and polysorbate 60. J Control Release. 2017;254:55–64.

    Article  CAS  PubMed  Google Scholar 

  74. Masuda I, et al. Gene transfer with liposomes to the intraocular tissues by different routes of administration. Invest Ophthalmol Vis Sci. 1996;37:1914–20.

    CAS  PubMed  Google Scholar 

  75. Michalakis S, et al. Gene therapy restores vision and delays degeneration in the CNGB1(−/−) mouse model of retinitis pigmentosa. Adv Exp Med Biol. 2014;801:733–9.

    Article  PubMed  Google Scholar 

  76. Millington-Ward S, et al. Strategems in vitro for gene therapies directed to dominant mutations. Hum Mol Genet. 1997;6:1415–26.

    Article  CAS  PubMed  Google Scholar 

  77. Mohan RR, et al. Corneal gene therapy: basic science and translational perspective. Ocul Surf. 2013;11:150–64.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Molday RS, Zhang K. Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration. Prog Lipid Res. 2010;49:476–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Naik R, et al. Gene delivery to the retina: focus on non-viral approaches. Drug Discov Today. 2009;14:306–15.

    Article  CAS  PubMed  Google Scholar 

  80. Ojeda E, et al. The in fluence of the polar head-group of synthetic cationic lipids on the transfection efficiency mediated by niosomes in rat retina and brain. Biomaterials. 2016;77:267–79.

    Article  CAS  PubMed  Google Scholar 

  81. Oliveira C, et al. Recent advances in characterization of nonviral vectors for delivery of nucleic acids: impact on their biological performance. Expert Opin Drug Deliv. 2015;12:27–39.

    Article  CAS  PubMed  Google Scholar 

  82. Oliveira AV, et al. Non-viral strategies for ocular gene delivery. Mater Sci Eng C Mater Biol Appl. 2017;77:1275–89.

    Article  CAS  PubMed  Google Scholar 

  83. Ou J, et al. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer. J Clin Invest. 2015;125:2891–903.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Park TK, et al. Intravitreal delivery of AAV8 retinoschisin results in cell type-specific gene expression and retinal rescue in the Rs1-KO mouse. Gene Ther. 2009;16:916–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Peeters L, et al. Vitreous: a barrier to nonviral ocular gene therapy. Invest Ophthalmol Vis Sci. 2005;46:3553–61.

    Article  PubMed  Google Scholar 

  86. Pensado A, et al. Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: an approach of gene therapy to treat retinitis pigmentosa. Nanomedicine. 2016;12:2251–60.

    Article  CAS  PubMed  Google Scholar 

  87. Petrs-Silva H, Linden R. Advances in gene therapy technologies to treat retinitis pigmentosa. Clin Ophthalmol. 2014;8:127–36.

    PubMed  Google Scholar 

  88. Rajala A, et al. Nanoparticle-assisted targeted delivery of eye-specific genes to eyes significantly improves the vision of blind mice in vivo. Nano Lett. 2014;14:5257–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Rodríguez-Gascón A, et al. Vaginal gene therapy. Adv Drug Deliv Rev. 2015;92:71–83.

    Article  PubMed  CAS  Google Scholar 

  90. Ruiz de Garibay AP, et al. Role of endocytic uptake in transfection efficiency of solid lipid nanoparticles-based nonviral vectors. J Gene Med. 2013;15:427–40.

    Article  CAS  PubMed  Google Scholar 

  91. Sikkink SK, et al. X-linked retinoschisis: an update. J Med Genet. 2007;44:225–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Sochor MA, et al. An autogenously regulated expression system for gene therapeutic ocular applications. Sci Report. 2015;5:17105.

    Article  CAS  Google Scholar 

  93. Solinís MA, et al. Treatment of ocular disorders by gene therapy. Eur J Pharm Biopharm. 2015;95:331–42.

    Article  PubMed  CAS  Google Scholar 

  94. Tantri A, et al. X-linked retinoschisis: a clinical and molecular genetic review. Surv Ophthalmol. 2004;49:214–30.

    Article  PubMed  Google Scholar 

  95. Thumann G. Prospectives for gene therapy of retinal degenerations. Curr Genomics. 2012;13:350–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Trapani I, et al. Vector platforms for gene therapy of inherited retinopathies. Prog Retin Eye Res. 2014;43:108–28.

    Article  CAS  PubMed  Google Scholar 

  97. Touchard E, et al. Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina. Mol Ther. 2012;20:1559–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Travis GH, et al. The retinal degeneration slow (rds) gene product is a photoreceptor discmembrane-associated glycoprotein. Neuron. 1991;6:61–70.

    Article  CAS  PubMed  Google Scholar 

  99. Van Lookeren Campagne M, et al. Mechanisms of age-related macular degeneration and therapeutic opportunities. J Pathol. 2014;232:151–64.

    Article  PubMed  Google Scholar 

  100. Wang Y, et al. Cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific cells of the retina in vivo. Theranostics. 2016;6:1514–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Wasungu L, Hoekstra D. Cationic lipids, lipoplexes and intracellular delivery of genes. J Control Release. 2006;116:255–64.

    Article  CAS  PubMed  Google Scholar 

  102. Weber BH, et al. Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure. Proc Natl Acad Sci U S A. 2002;99:6222–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yamada Y, et al. Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells. Biomaterials. 2015;52:189–98.

    Article  CAS  PubMed  Google Scholar 

  104. Yanik M, et al. In vivo genome editing as a potential treatment strategy for inherited retinal dystrophies. Prog Retin Eye Res. 2017;56:1–18.

    Article  CAS  PubMed  Google Scholar 

  105. Yin H, et al. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014;15:541–55.

    Article  CAS  PubMed  Google Scholar 

  106. Zhang Y, et al. Design and biophysical characterization of bioresponsive degradable poly(dimethylaminoethyl methacrylate) based polymers for in vitro DNA transfection. Biomacromolecules. 2012;13:313–22.

    Article  CAS  PubMed  Google Scholar 

  107. Zhu C, et al. Widespread expression of an exogenous gene in the eye after intravenous administration. Invest Ophthalmol Vis Sci. 2002;43:3075–80.

    PubMed  Google Scholar 

  108. Zulliger R, et al. Non-viral therapeutic approaches to ocular diseases: an overview and future directions. J Control Release. 2015;219:471–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the University of the Basque Country UPV/EHU (PPG17/65 and GIU17/032). J Torrecilla thanks UPV/EHU for her research grant.

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Authors and Affiliations

  1. Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain

    Ana del Pozo-Rodríguez, Josune Torrecilla, Alicia Rodríguez-Gascón & María Ángeles Solinís

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  1. Ana del Pozo-Rodríguez
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  2. Josune Torrecilla
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  3. Alicia Rodríguez-Gascón
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  4. María Ángeles Solinís
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Correspondence to María Ángeles Solinís .

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Editors and Affiliations

  1. Faculty of Pharmacy, Sankalchand Patel University, Gujarat, India

    Jayvadan K. Patel

  2. College of Pharmacy, University of South Florida, Tampa, FL, USA

    Vijaykumar Sutariya

  3. School of Medicine, Faculty of Health, Deakin University, Victoria, Australia

    Jagat Rakesh Kanwar

  4. College of Pharmacy, University of South Florida, Tampa, FL, USA

    Yashwant V. Pathak

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del Pozo-Rodríguez, A., Torrecilla, J., Rodríguez-Gascón, A., Solinís, M.Á. (2018). Nonviral Delivery Systems for Gene Therapy for Retina and Posterior Segment Disease. In: Patel, J., Sutariya, V., Kanwar, J., Pathak, Y. (eds) Drug Delivery for the Retina and Posterior Segment Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-95807-1_8

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