PNASJClub
A tetravalent bispecific protein enables targeted degradation of VCAM-1 and VEGFR for treatment of choroidal neovascularization.
Proceedings of the National Academy of Sciences · · Journal Article
Zhang, Du + more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
A tetravalent bispecific protein (RHV) enables concurrent lysosomal degradation of VCAM-1 and VEGFR in murine choroidal neovascularization, matching aflibercept efficacy at one-quarter molar dose.
- Why it matters: Anti-VEGF therapy leaves nearly 50% of wet AMD patients with incomplete responses and can cause off-target risks like geographic atrophy from non-specific VEGF blockade.
- What they did: The study engineered RHV on an L-rhamnulose-1-phosphate aldolase scaffold with VCAM-1- and VEGFR-binding peptides, then assessed receptor internalization, lysosomal degradation, and downstream signaling inhibition in AMD patient aqueous humor and murine CNV models.
- The result: In murine CNV, a single intravitreal RHV injection showed superior ocular retention and lesion penetration, sustaining inhibition of VEGF/VEGFR, PI3K/AKT, and Apelin/APJ pathways while achieving efficacy comparable to aflibercept at one-quarter of the molar dose.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.