Engineering Human Circulating Monocytes/Macrophages by Systemic Deliverable Gene Editing

• DOI: 10.3389/fimmu.2022.754557
• Publication Date: 2022-05-18T10:17:50Z
• Authors: So Yoon Lee; Javier Fierro; Jake Dipasquale; Anthony Bastian; An M. Tran; Deawoo Hong; Brandon Chin; Paul J. Nguyen-Lee; Sarah Mazal; Jamil Espinal; Tima Thomas; Huanyu Dou
• Keywords: Monocyte

Delivery of plasmid DNA to transfect human primary macrophages is extremely difficult, especially for genetic engineering. Engineering imperative the treatment many diseases including infectious diseases, cancer, neurological and aging. Unfortunately, does not cross nuclear membranes terminally differentiated integrate (pDNA) into their genome. To address this issue, we have developed a core-shell nanoparticle (NP) using our newly created cationic lipid deliver anti-inflammatory cytokine IL-4 pDNA (IL-4pDNA-NPs). Human blood monocyte-derived (MDM) were effectively transfected with IL-4pDNA-NPs. IL-4pDNA-NPs internalized in MDM within 30 minutes delivered nucleus 2 hours. Exogenous expression was detected 1 - days continued up days. Functional led M2 macrophage polarization vitro an vivo mouse model inflammation. These data suggest that these NPs can protect from degradation by nucleases once inside cell, transport enhance gene delivery . In research, new method plasmids monocytes gene-editing. Introducing provides therapy solution various diseases.