Title: Synthetic Monopartite Peptide That Enables the Nuclear Import of Genes Delivered by the Neurotensin-Polyplex Vector - PubMed URL Source: https://pubmed.ncbi.nlm.nih.gov/33125243/ Markdown Content: Actions . 2020 Dec 7;17(12):4572-4588. doi: 10.1021/acs.molpharmaceut.0c00755. Epub 2020 Oct 30. [Rasajna Nadella](https://pubmed.ncbi.nlm.nih.gov/?term=Nadella+R&cauthor_id=33125243)[2](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-2 "Biosciences, IIIT Srikakulam-RGUKT, Etcherla 532402, Srikakulam District, Andhra Pradesh, India."),[Minerva Maldonado-Berny](https://pubmed.ncbi.nlm.nih.gov/?term=Maldonado-Berny+M&cauthor_id=33125243)[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[Maria L Escobedo-Sanchez](https://pubmed.ncbi.nlm.nih.gov/?term=Escobedo-Sanchez+ML&cauthor_id=33125243)[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[Rosana Fiorentino-Pérez](https://pubmed.ncbi.nlm.nih.gov/?term=Fiorentino-P%C3%A9rez+R&cauthor_id=33125243)[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[Bismark Gatica-García](https://pubmed.ncbi.nlm.nih.gov/?term=Gatica-Garc%C3%ADa+B&cauthor_id=33125243)[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[Manuel A Fernandez-Parrilla](https://pubmed.ncbi.nlm.nih.gov/?term=Fernandez-Parrilla+MA&cauthor_id=33125243)[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[Moreno Mario Gil](https://pubmed.ncbi.nlm.nih.gov/?term=Mario+Gil+M&cauthor_id=33125243)[4](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-4 "Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[David Reyes-Corona](https://pubmed.ncbi.nlm.nih.gov/?term=Reyes-Corona+D&cauthor_id=33125243)[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[Ubaldo García](https://pubmed.ncbi.nlm.nih.gov/?term=Garc%C3%ADa+U&cauthor_id=33125243)[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico."),[Carlos E Orozco-Barrios](https://pubmed.ncbi.nlm.nih.gov/?term=Orozco-Barrios+CE&cauthor_id=33125243)[5](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-5 "Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Unidad de Investigaciones Médicas en Enfermedades Neurológicas, CONACyT, Av. Cuauhtémoc 330, Doctores, 06720 Ciudad de México, Mexico."),[Maria E Gutierrez-Castillo](https://pubmed.ncbi.nlm.nih.gov/?term=Gutierrez-Castillo+ME&cauthor_id=33125243)[6](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-6 "Departamento de Biociencias e Ingeniería, Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo, Instituto Politécnico Nacional, 30 de junio de 1520 s/n, La Laguna Ticoman, 07340 Ciudad de Mexico, Mexico."),[Daniel Martinez-Fong](https://pubmed.ncbi.nlm.nih.gov/?term=Martinez-Fong+D&cauthor_id=33125243)[1](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-1 "Programa de Doctorado en Nanociencias y Nanotecnología, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico.")[3](https://pubmed.ncbi.nlm.nih.gov/33125243/#full-view-affiliation-3 "Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Av. Instituto Politécnico Nacional, No. 2508, San Pedro Zacatenco, 07360 Ciudad de México, Mexico.") Affiliations * PMID: **33125243** * DOI: [10.1021/acs.molpharmaceut.0c00755](https://doi.org/10.1021/acs.molpharmaceut.0c00755) ## Synthetic Monopartite Peptide That Enables the Nuclear Import of Genes Delivered by the Neurotensin-Polyplex Vector Francisco E Lopez-Salas et al. Mol Pharm.2020. ## Abstract 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 to improving its therapeutic safety is replacing the viral karyophilic component (peptide KPSV40; MAPTKRKGSCPGAAPNKPK), which performs the nuclear import activity, by a shorter synthetic peptide (KPRa; KMAPKKRK). We explored this issue and the mechanism of plasmid DNA translocation through the expression of the green fluorescent protein or red fluorescent protein fused with KPRa and internalization assays and whole-cell patch-clamp configuration experiments in a single cell together with importin α/β pathway blockers. We showed that KPRa electrostatically bound to plasmid DNA increased the transgene expression compared with KPSV40 and enabled nuclear translocation of KPRa-fused red fluorescent proteins and plasmid DNA. Such translocation was blocked with ivermectin or mifepristone, suggesting importin α/β pathway mediation. KPRa also enabled NTS-polyplex-mediated expression of reporter or physiological genes such as human mesencephalic-derived neurotrophic factor (hMANF) in dopaminergic neurons in vivo. KPRa is a synthetic monopartite peptide that showed nuclear import activity in NTS-polyplex vector-mediated gene delivery. KPRa could also improve the transfection of other nonviral vectors used in gene therapy. **Keywords:** Parkinson’s disease; cancer; fusion proteins; gene therapy; importins; nonviral vectors. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [Improved neurotensin-vector-mediated gene transfer by the coupling of hemagglutinin HA2 fusogenic peptide and Vp1 SV40 nuclear localization signal.](https://pubmed.ncbi.nlm.nih.gov/12399111/) Navarro-Quiroga I, Antonio González-Barrios J, Barron-Moreno F, González-Bernal V, Martinez-Arguelles DB, Martinez-Fong D.Navarro-Quiroga I, et al.Brain Res Mol Brain Res. 2002 Sep 30;105(1-2):86-97. doi: 10.1016/s0169-328x(02)00396-0.Brain Res Mol Brain Res. 2002.PMID: 12399111 * [Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson's disease.](https://pubmed.ncbi.nlm.nih.gov/26198255/) Hernandez-Chan NG, Bannon MJ, Orozco-Barrios CE, Escobedo L, Zamudio S, De la Cruz F, Gongora-Alfaro JL, Armendáriz-Borunda J, Reyes-Corona D, Espadas-Alvarez AJ, Flores-Martínez YM, Ayala-Davila J, Hernandez-Gutierrez ME, Pavón L, García-Villegas R, Nadella R, Martinez-Fong D.Hernandez-Chan NG, et al.J Biomed Sci. 2015 Jul 22;22(1):59. doi: 10.1186/s12929-015-0166-7.J Biomed Sci. 2015.PMID: 26198255 Free PMC article. * [Regulation of human GDNF gene expression in nigral dopaminergic neurons using a new doxycycline-regulated NTS-polyplex nanoparticle system.](https://pubmed.ncbi.nlm.nih.gov/28219741/) Espadas-Alvarez AJ, Bannon MJ, Orozco-Barrios CE, Escobedo-Sanchez L, Ayala-Davila J, Reyes-Corona D, Soto-Rodriguez G, Escamilla-Rivera V, De Vizcaya-Ruiz A, Eugenia Gutierrez-Castillo M, Padilla-Viveros A, Martinez-Fong D.Espadas-Alvarez AJ, et al.Nanomedicine. 2017 May;13(4):1363-1375. doi: 10.1016/j.nano.2017.02.006. 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