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Green Transfection: Cationic Lipid Nanocarrier System Derivatized from Vegetable Fat, Palmstearin Enhances Nucleic Acid Transfections.
ACS Omega ( IF 3.7 ) Pub Date : 2017-11-14 00:00:00 , DOI: 10.1021/acsomega.7b00935 Priya Dharmalingam 1 , Hari Krishna R Rachamalla 2 , Brijesh Lohchania 1 , Bhanuprasad Bandlamudi 1 , Saravanabhavan Thangavel 1 , Mohankumar K Murugesan 1 , Rajkumar Banerjee 2, 3 , Arabinda Chaudhuri 2, 3 , Chandrashekhar Voshavar 2 , Srujan Marepally 1
ACS Omega ( IF 3.7 ) Pub Date : 2017-11-14 00:00:00 , DOI: 10.1021/acsomega.7b00935 Priya Dharmalingam 1 , Hari Krishna R Rachamalla 2 , Brijesh Lohchania 1 , Bhanuprasad Bandlamudi 1 , Saravanabhavan Thangavel 1 , Mohankumar K Murugesan 1 , Rajkumar Banerjee 2, 3 , Arabinda Chaudhuri 2, 3 , Chandrashekhar Voshavar 2 , Srujan Marepally 1
Affiliation
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Cationic lipid-guided nucleic acid delivery holds great promise in gene therapy and genome-editing applications for treating genetic diseases. However, the major challenge lies in achieving therapeutically relevant efficiencies. Prior findings, including our own, demonstrated that asymmetry in the hydrophobic core of cationic lipids imparted superior transfection efficiencies. To this end, we have developed a lipid nanocarrier system with an asymmetric hydrophobic core (PS-Lips) derived from a mixture of fatty acids of food-grade palmstearin and compared its efficiency with symmetric palmitic acid-based nanocarrier system (P-Lip). PS-Lips exhibited superior transfection efficiencies with both plasmid DNA (pDNA) and mRNA in multiple cultured cells than the control P-Lip. More importantly, PS-Lips exhibited 2-fold superior transfections with linear nucleic acid, green fluorescent protein (GFP) mRNA in hematopoietic cells, when compared with the commercial control lipofectamine RNAiMAX. PS-Lips was also found to be effective in delivering genome-editing tools (CRISPR/Cas9, sgRNA encoded pDNA with a reporter GFP construct) than P-Lip in HEK-293 cells. In the present study, we report that cationic liposomes derivatized from natural food-grade fat palmstearin with a natural hydrophobic core asymmetry are efficient in delivering both linear and circular nucleic acids. In particular, PS-Lips is efficient in delivering mRNA to hematopoietic cells. These findings can be further exploited in the genome-editing approach for treating β-globinopathies.
中文翻译：
绿色转染：从植物脂肪衍生的阳离子脂质纳米载体系统，棕榈硬脂精可增强核酸转染。
阳离子脂质引导的核酸递送在治疗遗传疾病的基因治疗和基因组编辑应用中具有广阔的前景。然而，主要挑战在于实现与治疗有关的效率。先前的发现，包括我们自己的发现，表明阳离子脂质疏水核心的不对称性赋予了卓越的转染效率。为此，我们开发了具有不对称疏水核（PS-Lips）的脂质纳米载体系统，该非对称疏水核衍生自食品级棕榈硬脂酸的脂肪酸混合物，并将其效率与基于对称棕榈酸的纳米载体系统（P-Lip）进行了比较。 。PS-嘴唇在多重培养的细胞中，质粒DNA（pDNA）和mRNA的转染效率均优于对照P-Lip。更重要的是，与市售对照脂质转染胺RNAiMAX相比，PS-Lips在造血细胞中表现出2倍的线性核酸，绿色荧光蛋白（GFP）mRNA优异的转染效果。与P-Lip相比，PS-Lips还可以有效地提供基因组编辑工具（CRISPR / Cas9，带有报告子GFP构建体的sgRNA编码的pDNA）。在HEK-293细胞中。在本研究中，我们报道了从天然食品级脂肪棕榈硬脂精衍生而来的阳离子脂质体，具有天然疏水核心不对称性，可有效递送线性和环状核酸。特别地，PS-Lips有效地将mRNA递送至造血细胞。这些发现可以在基因组编辑方法中进一步用于治疗β-球蛋白病。
更新日期：2017-11-14
中文翻译：
绿色转染：从植物脂肪衍生的阳离子脂质纳米载体系统，棕榈硬脂精可增强核酸转染。
阳离子脂质引导的核酸递送在治疗遗传疾病的基因治疗和基因组编辑应用中具有广阔的前景。然而，主要挑战在于实现与治疗有关的效率。先前的发现，包括我们自己的发现，表明阳离子脂质疏水核心的不对称性赋予了卓越的转染效率。为此，我们开发了具有不对称疏水核（PS-Lips）的脂质纳米载体系统，该非对称疏水核衍生自食品级棕榈硬脂酸的脂肪酸混合物，并将其效率与基于对称棕榈酸的纳米载体系统（P-Lip）进行了比较。 。PS-嘴唇在多重培养的细胞中，质粒DNA（pDNA）和mRNA的转染效率均优于对照P-Lip。更重要的是，与市售对照脂质转染胺RNAiMAX相比，PS-Lips在造血细胞中表现出2倍的线性核酸，绿色荧光蛋白（GFP）mRNA优异的转染效果。与P-Lip相比，PS-Lips还可以有效地提供基因组编辑工具（CRISPR / Cas9，带有报告子GFP构建体的sgRNA编码的pDNA）。在HEK-293细胞中。在本研究中，我们报道了从天然食品级脂肪棕榈硬脂精衍生而来的阳离子脂质体，具有天然疏水核心不对称性，可有效递送线性和环状核酸。特别地，PS-Lips有效地将mRNA递送至造血细胞。这些发现可以在基因组编辑方法中进一步用于治疗β-球蛋白病。
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