Current Designs of Polymeric Platforms Towards the Delivery of Nucleic Acids Inside the Cells with Focus on Polyethylenimine

Author(s)

de Oliveira, Fernando A. ^[1] ; Albuquerque, Lindomar J. C. ^[1] ; Delecourt, Gwendoline ^[2] ; Bennevault, Veronique ^{[2, 3]} ; Guegan, Philippe ^[2] ; Giacomelli, Fernando C. ^{[1, 2]}

Affiliation

^[1] Fed Univ ABC, Ctr Ciencias Naturais Humanas, Santo Andre, SP - Brazil

^[2] Sorbonne Univ, Inst Parisien Chim Mol Equipe Chim Polymeres, CNRS, UMR 8232, 4 Pl Jussieu, F-75252 Paris - France

^[3] Univ Paris Saclay, Univ Evry Val Essonne, Rue Pere Jarlan, F-91025 Evry - France

• Document type: Review article
• Source: CURRENT GENE THERAPY; v. 21, n. 5, p. 431-451, 2021.
• Web of Science Citations: 1

Abstract

Background: Gene delivery is a promising technology for treating diseases linked to abnormal gene expression. Since nucleic acids are the therapeutic entities in such approach, a transfecting vector is required because the macromolecules are not able to efficiently enter the cells by themselves. Viral vectors have been evidenced to be highly effective in this context; however, they suffer from fundamental drawbacks, such as the ability to stimulate immune responses. The development of synthetic vectors has accordingly emerged as an alternative. Objectives: Gene delivery by using non-viral vectors is a multi-step process that poses many challenges, either regarding the extracellular or intracellular media. We explore the delivery pathway and afterwards, we review the main classes of non-viral gene delivery vectors. We further focus on the progresses concerning polyethylenimine-based polymer-nucleic acid polyplexes, which have emerged as one of the most efficient systems for delivering genetic material inside the cells. Discussion: The complexity of the whole transfection pathway, along with a lack of fundamental understanding, particularly regarding the intracellular trafficking of nucleic acids complexed to non-viral vectors, probably justifies the current (beginning of 2021) limited number of formulations that have progressed to clinical trials. Truly, successful medical developments still require a lot of basic research. Conclusion: Advances in macromolecular chemistry and high-resolution imaging techniques will be useful to understand fundamental aspects towards further optimizations and future applications. More investigations concerning the dynamics, thermodynamics and structural parameters of polyplexes would be valuable since they can be connected to the different levels of transfection efficiency hitherto evidenced. (AU)

• FAPESP's process: 16/23844-8 - Biodegradable and pH-responsive polymersomes for gene and protein delivery
• Grantee: Lindomar Jose Calumby Albuquerque
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/11038-2 - Polymer colloids in biological environments: from Polymer Synthesis to nanobiointerfaces
• Grantee: Fernando Carlos Giacomelli
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 19/20470-8 - Environmentally-responsive supramolecular polymeric assemblies for the intracellular delivery of therapeutic DNA: towards a toolbox for novel generation of nanopharmaceuticals in ophthalmology
• Grantee: Fernando Carlos Giacomelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/12944-0 - Structural and biological evaluations of polyplexes obtained by the complexation of DNA and polyethylenimine derivatives containing alkyl chains and lactose towards the treatment of genetic eye disorders
• Grantee: Fernando Augusto de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate