Effective gene-delivery systems for primary human T cell engineering are useful tools for both basic research and clinical immunotherapy applications. Pseudovirus-based systems and electro-transfection are the most popular strategies for genetic material transduction. Compared with viral-particle-mediated approaches, electro-transfection is safer, with a faster process time, and lower cost. However, this method is associated with low cell yields and is laborious due to multiple handling steps. Lipid nanoparticles (LNP) have emerged as a highly effective tool for nucleic acid delivery in vivo, yet have been difficult to demonstrate delivery to primary T-cells. Here we demonstrate the development of a novel LNP composed of biodegradable COATSOME® SS-Series that provide high level of gene transfection into human primary T-cells ex-vivo with a rapid single step transfection protocol. Compared to electroporation, the expression of an mRNA luciferase reporter was 13 fold higher in CD3+ activated human primary T-cells. The COATSOME® SS-Series were also evaluated in vivo with single doses up to 124 mg./kg being well tolerated in mice. We also describe efforts to lower the cellular toxicity of ionizable lipids through improvements in biodegradable characteristics. Additional improvements in the design were undertaken to reduce the immunogenicity of ionizable lipids. Together these approaches can enable the accelerated development and manufacturing of cell therapies.