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Lentiviral delivered aflibercept OXB-203 for treatment of neovascular AMD

Authors :
Sharifah Iqball
Daniel K. Beck
Gayathri Devarajan
Cheen P. Khoo
Deirdre M. O’Connor
Scott Ellis
Efrain Guzman
Kyriacos A. Mitrophanous
Yatish Lad
Source :
Molecular Therapy: Methods & Clinical Development, Vol 30, Iss , Pp 350-366 (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in the aging population, with vascular endothelial growth factor (VEGF) playing a key role. Treatment with recombinant anti-VEGFs is the current standard of care; however, it is only effective for 1–2 months at a time and requires re-administration. Gene therapy could pave the way for stable, long-term expression of therapeutic anti-VEGF with a single dose, reducing the frequency of treatment and potentially improving clinical outcomes. As such, we have developed OXB-203, a lentiviral-based gene therapy encoding the anti-VEGF protein aflibercept. Aflibercept derived from OXB-203 exhibited comparable in vitro binding characteristics to VEGF as recombinant aflibercept. Furthermore, its biological potency was demonstrated by the equivalent inhibition of VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and tubule formation as recombinant aflibercept. In a rat choroidal neovascularization (CNV) model of nAMD, a single subretinal administration of OXB-203 reduced laser-induced CNV lesion areas analogous to an intravitreal bolus of recombinant aflibercept. Finally, in a head-to-head comparative study, aflibercept derived from OXB-203 was shown to be expressed at significantly higher levels in ocular tissues than from an AAV8-aflibercept vector following a single subretinal delivery to rats. These findings support the therapeutic potential of OXB-203 for the management of nAMD.

Details

Language :
English
ISSN :
23290501
Volume :
30
Issue :
350-366
Database :
Directory of Open Access Journals
Journal :
Molecular Therapy: Methods & Clinical Development
Publication Type :
Academic Journal
Accession number :
edsdoj.bf9e54c2315e4b6d9e5ed33512f892a1
Document Type :
article
Full Text :
https://doi.org/10.1016/j.omtm.2023.07.001