Green Transfection: Cationic Lipid Nanocarrier System Derivatized from Vegetable Fat, Palmstearin Enhances Nucleic Acid Transfections.
Green Transfection: Cationic Lipid Nanocarrier System Derivatized from Vegetable Fat, Palmstearin Enhances Nucleic Acid Transfections.
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DOI：
10.1021/acsomega.7b00935
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发表时间：
2017-11-30
期刊：
影响因子：
4.1
通讯作者：
Marepally S
中科院分区：
文献类型：
--
作者：
Dharmalingam P;Rachamalla HKR;Lohchania B;Bandlamudi B;Thangavel S;Murugesan MK;Banerjee R;Chaudhuri A;Voshavar C;Marepally S
阳离子脂质引导的核酸递送在用于治疗遗传疾病的基因治疗和基因组编辑应用中具有巨大的前景。然而，主要的挑战在于实现治疗相关的效率。先前的发现，包括我们自己的，证明了阳离子脂质的疏水核心的不对称性赋予了上级转染效率。为此，我们开发了一种脂质纳米载体系统，该系统具有来自食品级棕榈硬脂酸的脂肪酸混合物的不对称疏水核心（PS-Lips），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-Lip在多个培养细胞中表现出比对照P-Lip上级的质粒DNA（pDNA）和mRNA转染效率。更重要的是，当与商业对照lipofectamine RNAiMAX相比时，PS-Lips在造血细胞中表现出2倍上级的线性核酸、绿色荧光蛋白（GFP）mRNA的转染。还发现PS-Lips在HEK-293细胞中比P-Lip更有效地递送基因组编辑工具（CRISPR/Cas9，具有报告GFP构建体的sgRNA编码的pDNA）。在本研究中，我们报告了从天然食品级脂肪棕榈硬脂酸衍生的具有天然疏水核心不对称性的阳离子脂质体在递送线性和环状核酸方面是有效的。特别是，PS-Lips在将mRNA递送至造血细胞方面是有效的。这些发现可以进一步用于治疗β-球蛋白病的基因组编辑方法。
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.
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影响因子：
46.9
作者：
Heck, Dirk;Kowalczyk, Monika S.;Yudovich, David;Belizaire, Roger;Puram, Rishi V.;McConkey, Marie E.;Thielke, Anne;Aster, Jon C.;Regev, Aviv;Ebert, Benjamin L.
通讯作者：
Ebert, Benjamin L.
影响因子：
7.3
作者：
Karmali, PP;Kumar, VV;Chaudhuri, A
通讯作者：
Chaudhuri, A
影响因子：
14
作者：
Mukthavaram, Rajesh;Marepally, Srujan;Chaudhuri, Arabinda
通讯作者：
Chaudhuri, Arabinda
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
4.7
作者：
Chandrashekhar, Voshavar;Srujan, Marepally;Chaudhuri, Arabinda
通讯作者：
Chaudhuri, Arabinda