Carbosilane dendrimers as gene delivery agents for the treatment of HIV infection

✍ Scribed by Perisé-Barrios, Ana Judith; Jiménez, José Luis; Domínguez-Soto, Angeles; de la Mata, F. Javier; Corbí, Angel L.; Gomez, Rafael; Muñoz-Fernandez, María Ángeles

• Book ID: 121750011
• Publisher: Elsevier Science
• Year: 2014
• Tongue: English
• Weight: 720 KB
• Volume: 184
• Category: Article
• ISSN: 0168-3659
• DOI: 10.1016/j.jconrel.2014.03.048

✦ Synopsis

Despite the use of siRNA in the downregulation of HIV-1 replication which has been reported, CD4 T lymphocytes are difficult to transfect with non-viral vectors. We determined whether second generation carbosilane dendrimers (2G-NN16 and 2G-03NN24) may be efficient transfectants in CD4 T lymphocytes. Dendrimers were also tested on macrophages to determine whether they can modify macrophage phenotype and induce an inflammatory response. The nanoconjugate formed by 2G-03NN24/siRNA-Nef presents the highest inhibition of HIV-1 replication. Dendrimers presented safety properties because they did not induce proliferation on CD4 T lymphocytes and decrease the release of TNFα and IL-12p40 by macrophages. Both dendrimers also decrease the phagocytosis activity. Additionally, 2G-03NN24 dendrimer decreases the CCL2 and CCR2 expression in macrophages. Carbosilane dendrimers 2G-NN16 and 2G-03NN24 can be used as efficient non-viral vectors for gene therapy applications, mainly in the treatment of HIV infection.