The efficiency of gene transfer and the level of protein production are significantly dependent on the transport systems. Despite the ability of chemical systems to deliver genes into the cell, the excessive toxicity of these methods for use in clinical trials confronts with limitations. Recent advances in microfluidic systems have created an exciting prospect for gene delivery. Microfluidic systems, with precise control and optimization of multiple processes, provide gene delivery and drug delivery into the cells. These processes can include a variety of physical fields such as cell compression, electric and thermal field, which destabilize the phospholipid membrane of cell and induce the stimuli for gene transfer into the cell .In addition, microfluidic systems have been used in a variety of other fields, such as the pharmaceutical industry, chemical and biomedical sensors and the development of cell-based vaccines. Dendritic cells (DCs) as antigen presenting cells can induce the cellular immune response. Hence, DC- based vaccines have been introduced as a new therapeutic strategy for cancer treatment. The studies indicated that the efficiency of gene delivery in DCs is very low; thus, some combinatorial physical approaches can increase the efficiency of gene delivery in these cells. The aim of this study is the design of a microfluidic system by applying mechanical and thermal approaches to transfer the Nef, Nef-Hsp70 and Nef-Hsp27 genes into dendritic cells. The Nef protein of HIV-1 virus due to its expression in the first phase of infection and having numerous roles including inhibition of CD4 receptors, MHC, stimulation of virus replication and infection was known as an antigenic candidate for the development of therapeutic vaccines against HIV-1. Moreover, heat shock proteins (HSPs) are stress proteins that have multiple roles such as chaperon activity and anti-apoptotic properties. In addition to the protective roles of heat shock proteins in the cytosol, these proteins such as Hsp70 and Hsp27 play a key role in stimulating the immune system when they are in the extracellular space. One of these roles is their ability to participate in antigen delivery activity as an adjuvant. In this study, it is promising that by designing a microfluidic device in comparison with chemical system to deliver antigen-encoding DNA to immune cells, a novel strategy was developed for the optimization of cell-based vaccines against HIV infection.
