Discovering Peptides that Target Specific Cells in Blood Vessel Abnormalities

Blood and lymphatic vessel problems, like venous malformations (VMs), can happen when cells involved in blood vessel growth go awry. These issues often stem from problems with the Angiopoietin/TIE2-PI3K/AKT/mTOR signaling pathway, with a common mutation being TIE2 L914F. Treating these problems by targeting this pathway could be beneficial, but it's better to focus treatments only on the affected areas. To find peptides that can bind selectively to TIE2 L914F lesions, scientists used a method called in vivo phage display. They looked at how different phages interacted with mouse cells expressing TIE2 L914F in a subcutaneous matrigel model. By combining this process with subcellular fractionation, they could identify potential cell-penetrating phages. Advanced technology like Next Generation Sequencing (NGS) and bioinformatics helped them analyze the phages and find new cell-penetrating peptides (CPPs). They grouped similar CPPs into clusters to pick the most promising ones. These chosen CPPs could enter human endothelial cells in lab cultures and delivered siRNA inside, showing their potential for targeted therapies. This study highlights how modern scientific tools can help find tailored treatments for blood vessel abnormalities.