Development of gene delivery vectors based on dynein light chain Rp3 and T22 peptide for CXCR4+-based cell targeting

• Grant number: 15/20193-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): January 05, 2016
• Effective date (End): December 21, 2016
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Adriano Rodrigues Azzoni
• Grantee: Marianna Teixeira de Pinho Favaro
• Supervisor: Neus Ferrer-Miralles
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Universitat Autònoma de Barcelona (UAB), Spain
• Associated to the scholarship: 12/18850-8 - Development and in vitro and in vivo evaluation of gene delivery vectors based on dynein light chain Rp3 and synthetic peptides., BP.DR

Abstract

The definition of an ideal gene delivery vector has recently been modified to include cell targeting as a major issue. Our group has developed a recombinant dynein-based vector, T-Rp3, which proved to be very efficient for cell uptake and intracellular trafficking, but its in vivo application may be severely limited by its lack of cell specificity. In this context, our recent collaboration with Nanobiotechnology group at UAB, Spain, opens doors to a further step in our purpose of developing protein vectors that can mimic viral vectors. Our experience with T-Rp3 can now be complemented by their expertise in developing targeted delivery systems, allowing the assemble of a chimeric protein composed by dynein light chain Rp3 and T22, a peptide that binds C-X-C chemokine receptor type 4 (CXCR4) and promotes internalization in a specific manner. The CXCR4 receptor has an important role in malignant cells, since it is known to be overexpressed in 23 different cancer types, but not in normal cells counterparts. The proposed protein, T22-Rp3, is expected to efficiently transfect CXCR4-expressing cells. In this BEPE research project, we propose to clone, produce and characterize the T22-Rp3 recombinant protein with the aim to add significant cell targeting ability to the T-RP3 prototype. In vitro transfection of colorectal adenocarcinoma cells (SW1417), among others, will evaluate the protein's potential to deliver plasmid DNA (pDNA) as well as siRNA. By this way, we expect to consolidate a new collaboration and to move one step further in exploring the abilities of dynein-based vectors in search of an efficient non-viral gene delivery vector. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE PINHO FAVARO, MARIANNA TEIXEIRA; SANCHEZ-GARCIA, LAURA; SANCHEZ-CHARDI, ALEJANDRO; ROLDAN, MONICA; UNZUETA, UGUTZ; SERNA, NAROA; CANO-GARRIDO, OLIVIA; AZZONI, ADRIANO RODRIGUES; FERRER-MIRALLES, NEUS; VILLAVERDE, ANTONIO; et al. Protein nanoparticles are nontoxic, tuneable cell stressors. Nanomedicine, v. 13, n. 3, p. 255-268, FEB 2018. (15/20193-3)