In this opinion article we critically assess evidence for the existence of a family of antiangiogenic vascular endothelial growth factor (Vegfaxxxb) transcripts, arising from the use of a phylogenetically conserved alternative distal splice site within exon 8 of the VEGFA gene. We explain that prior evidence for Vegfaxxxb transcripts in tissues rests heavily upon flawed RT-PCR methodologies, with the extensive use of 5'-tailing in primer design being the main issue. Furthermore, our analysis of large RNA-seq data sets (human and ovine) fails to identify a single Vegfaxxxb transcript. Therefore, we challenge the very existence of Vegfaxxxb transcripts, which further questions the physiological relevance of studies based on the use of 'anti-VEGFAxxxb' antibodies. Our analysis has implications for the proposed therapeutic use of isoform-specific anti-VEGFA strategies for treating cancer and retinopathies.

中文翻译：

---

揭穿内源性抗血管生成 Vegfaxxxb 转录本的神话

在这篇意见文章中，我们批判性地评估了存在抗血管生成血管内皮生长因子 (Vegfaxxxb) 转录本家族的证据，这些转录本源于使用 VEGFA 基因外显子 8 内的系统发育保守的替代远端剪接位点。我们解释说，组织中 Vegfaxxxb 转录物的先前证据严重依赖于有缺陷的 RT-PCR 方法，主要问题是在引物设计中广泛使用 5'-拖尾。此外，我们对大型 RNA-seq 数据集（人和羊）的分析未能识别出单个 Vegfaxxxb 转录本。因此，我们挑战了 Vegfaxxxb 转录本的存在，这进一步质疑了基于使用“抗 VEGFAxxxb”抗体的研究的生理相关性。