Dendrimer delivery of an anti-VEGF oligonucleotide into the eye : a long term study into inhibition of laser induced CNV, distribution, uptake and toxicity

R.J. Marano, I. Toth, N. Wimmer, M. Brankov, Elizabeth Rakoczy

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

We have performed a long-term study into the use of a lipophilic amino-acid dendrimer to deliver an anti-vascular endothelial growth factor (VEGF) oligonucleotide (ODN-1) into the eyes of rats and inhibit laser-induced choroidal neovascularization (CNV). In addition, the uptake, distribution and retinal tolerance of the dendrimer plus oligonucleotide conjugates were examined. Analysis of fluorescein angiograms of laser photocoagulated eyes revealed that dendrimer plus ODN-1 significantly inhibited (P0.05) in mean severity score at 2 months (2.860.09), 4 months (2.150.17) or 6 months (2.70.12) compared to the vehicle-injected controls. Furthermore, we showed that intravitreally injected ODN-1 tagged with 6-fam was absorbed by a wide area of the retina and penetrated all of the retinal cell layers to the retinal pigment epithelium. Ophthalmological examinations indicated that the dendrimers plus ODN-1 conjugates were well tolerated in vivo, which was later confirmed using immunohistochemistry, which showed no observable increase in antigens associated with inflammation. We conclude that the use of such dendrimers may provide a viable mechanism for the delivery of therapeutic oligonucleotides for the treatment of angiogenic eye diseases.
Original languageEnglish
Pages (from-to)1514-1550
JournalGene Therapy
Volume12
Issue number21
DOIs
Publication statusPublished - 2005

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