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

Marano, R. J., Toth, I., Wimmer, N., Brankov, M. and Rakoczy, E. P. (2005) Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: A long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity. Gene Therapy, 12 21: 1544-1550. doi:10.1038/sj.gt.3302579


Author Marano, R. J.
Toth, I.
Wimmer, N.
Brankov, M.
Rakoczy, E. P.
Title Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: A long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity
Journal name Gene Therapy   Check publisher's open access policy
ISSN 0969-7128
1476-5462
Publication date 2005-11-01
Sub-type Article (original research)
DOI 10.1038/sj.gt.3302579
Volume 12
Issue 21
Start page 1544
End page 1550
Total pages 7
Place of publication Basingstoke, U.K.
Publisher Nature Publishing Group
Language eng
Subject 320500 Pharmacology and Pharmaceutical Sciences
250302 Biological and Medical Chemistry
270801 Gene Therapy
C1
730111 Hearing, vision, speech and their disorders
0604 Genetics
Formatted 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 (P<0.05) the development of CNV for 4-6 months by up to 95% in the initial stages. Eyes similarly injected with ODN-1 alone showed no significant difference (P>0.05) in mean severity score at 2 months (2.86±0.09), 4 months (2.15±0.17) or 6 months (2.7±0.12) 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.
© 2005 Nature Publishing Group All rights reserved.
Keyword Dendrimer
Oligonucleotide
VEGF
Neovascularization
Angiogenesis
Laser photocoagulation
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2006 Higher Education Research Data Collection
School of Pharmacy Publications
 
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