Retinol-binding protein 4 mRNA (RBP4 mRNA) (RBP4 mRNA)

Retinol-binding protein 4 (RBP4) mRNA is the messenger RNA transcript that encodes the RBP4 protein, the sole specific carrier for retinol (vitamin A) in the systemic circulation (UniProt: P02753). Synthesized primarily in the liver, this mRNA is a critical regulatory point for controlling the amount of retinol available to peripheral tissues, including the eye. In the context of metabolic health, overproduction of RBP4 mRNA is associated with insulin resistance and the development of type 2 diabetes (PubMed: 15951804). In ophthalmology, the RBP4 protein translated from this mRNA delivers retinol to the visual cycle, where excess retinol can lead to the accumulation of toxic bisretinoids like A2E in the retina. These toxins are the primary drivers of retinal degeneration in Stargardt disease and geographic atrophy (PubMed: 35143456). Therapeutic targeting of RBP4 mRNA using antisense oligonucleotides, such as GSK4532990, induces the degradation of the transcript via RNase H1. This reduction in mRNA levels leads to a significant decrease in hepatic RBP4 protein secretion and a subsequent lowering of circulating retinol levels. By limiting the supply of retinol to the eye, this mechanism aims to slow the progression of vision loss in patients with macular dystrophies (ClinicalTrials.gov: NCT04489511).

Other names

Retinol-binding protein 4 transcriptRBP4 messenger RNARBP4 gene transcriptPlasma retinol-binding protein mRNA

Antisense oligonucleotide-mediated degradation of mRNA via RNase H1, leading to reduced translation of Retinol-binding protein 4.