Synthetic Monopartite Peptide That Enables the Nuclear Import of Genes Delivered by the Neurotensin-Polyplex Vector

• DOI: 10.1021/acs.molpharmaceut.0c00755
• Publication Date: 2020-10-30T19:47:50Z
• Authors: Francisco E. Lope...; Rasajna Nadella; Minerva Maldonado...; Maria L. Escobedo...; Rosana Fiorentino...; Bismark Gatica-Ga...; Manuel A. Fernand...; Moreno Mario Gil; David Reyes-Corona; Ubaldo García; Carlos E. Orozco-...; Maria E. Gutierre...; Daniel Martinez-Fong
• Keywords: Internalization; NLS; Importin

Neurotensin (NTS)-polyplex is a multicomponent nonviral vector that enables gene delivery via internalization of the neurotensin type 1 receptor (NTSR1) to dopaminergic neurons and cancer cells. An approach improving its therapeutic safety replacing viral karyophilic component (peptide KPSV40; MAPTKRKGSCPGAAPNKPK), which performs nuclear import activity, by shorter synthetic peptide (KPRa; KMAPKKRK). We explored this issue mechanism plasmid DNA translocation through expression green fluorescent protein or red fused with KPRa assays whole-cell patch-clamp configuration experiments in single cell together importin α/β pathway blockers. showed electrostatically bound increased transgene compared KPSV40 enabled KPRa-fused proteins DNA. Such was blocked ivermectin mifepristone, suggesting mediation. also NTS-polyplex-mediated reporter physiological genes such as human mesencephalic-derived neurotrophic factor (hMANF) vivo. monopartite activity NTS-polyplex vector-mediated delivery. could improve transfection other vectors used therapy.