In NF1 tumors, where the NF1 gene alterations function as the initiating and key driver mutation, gene therapy holds enormous promise, but faces two main challenges: firstly, the very large size of NF1 gene of over 8400 bp that exceeds the packaging limit of AAV vectors11 and secondly, the weak tropism of natural occurring AAV serotypes with NF1 tumors12,13. This evidence concerns the gene NF1 and neurofibromatosis type 1.