Dataset Information

Virus-like Nonvirus Cationic Liposome for Efficient Gene Delivery via Endoplasmic Reticulum Pathway.

ABSTRACT: Gene vectors play a critical role in gene therapy. To achieve efficient transfection, we developed a novel nonvirus cationic liposome (Lipo-Par), which was bound covalently with the cationic polypeptide pardaxin (Par). Interestingly, the Lipo-Pars exhibited highly enhanced gene transfection efficiency in various cell lines compared to that of the non-Par-bonded liposomes (Lipo-Nons). As a result, the internalization and intracellular transport mechanisms of the Lipo-Pars were investigated, and the findings indicated their ability to actively target the endoplasmic reticulum (ER) by moving along the cell cytoskeleton after undergoing caveolin-mediated endocytosis. This intracellular transport process is similar to that of some viruses. It was also found that ER stress and calcium level disturbances can affect the Lipo-Par-mediated expression of certain exogenous genes. A possible, yet non-negligible explanation for the high transfection efficiency of the Lipo-Par is its virus-like intracellular behavior and the intimate relationship between the ER membrane and the nuclear envelope.

SUBMITTER: Yuan X

PROVIDER: S-EPMC7047280 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Virus-like Nonvirus Cationic Liposome for Efficient Gene Delivery via Endoplasmic Reticulum Pathway.

Yuan Xiaoling X Qin Bing B Yin Hang H Shi Yingying Y Jiang Mengshi M Luo Lihua L Luo Zhenyu Z Zhang Junlei J Li Xiang X Zhu Chunqi C Du Yongzhong Y You Jian J

ACS central science 20200211 2

Gene vectors play a critical role in gene therapy. To achieve efficient transfection, we developed a novel nonvirus cationic liposome (Lipo-Par), which was bound covalently with the cationic polypeptide pardaxin (Par). Interestingly, the Lipo-Pars exhibited highly enhanced gene transfection efficiency in various cell lines compared to that of the non-Par-bonded liposomes (Lipo-Nons). As a result, the internalization and intracellular transport mechanisms of the Lipo-Pars were investigated, and t ...[more]

PMID: 32123735

Similar Datasets

Project description:The chemokine stromal cell-derived factor (SDF)-1?/CXCL12 and its receptor CXC chemokine receptor 4 (CXCR4) play a crucial role in the homing/engraftment and retention of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow. It has been shown using the viral gene transfer technique that CXCR4 overexpression on human CD34(+) HSPC significantly improves their engraftment in murine models. However, clinical trials with gene therapy have revealed safety concerns related to the immunogenicity of the viral carriers, due to the random integration of viral genes into the host genome. Therefore, a method for CXCR4 gene delivery into HSPC that is safe, nonviral, and highly efficient is needed to improve clinical transplantation and gene therapies. In this work, we investigated the nonviral CXCR4 gene delivery into HSPC using the cationic liposome agent IBAfect. We used CD34(+) cells from cord blood and the models of immature hematopoietic cells expressing CD34 antigen, namely, leukemic cell lines KG-1a and KG-1. Transfection efficiency was determined by flow cytometric analysis 12, 24, 48, and 72 h after transfection, and the viability of cells analyzed by trypan blue exclusion and MTS assays. The functional response of CXCR4-transfected HSPC toward an SDF-1? gradient was determined by chemotaxis assay. We found that ~25% transfection is achieved for KG-1a and KG-1 cells and 20% for HSPC, and that the viability of CXCR4-transfected HSPC is not significantly altered. More importantly, overexpression of CXCR4 using IBAfect significantly increased the chemotaxis of KG-1 cells and HSPC toward SDF-1?. However, we tested 2 other commercially available cationic liposomes (Lipofectamine 2000 and 1,2-dioleoyl-3-trimethylammonium-propane [DOTAP]) in parallel, and we found that they failed to deliver the CXCR4 gene into cells under the same conditions. These results suggest that IBAfect-mediated in vitro gene delivery to overexpress CXCR4 on HSPC is a safe and efficient technique with great potential for improving the efficacy of HSPC transplantation and gene therapy protocols.

Dataset Information

Virus-like Nonvirus Cationic Liposome for Efficient Gene Delivery via Endoplasmic Reticulum Pathway.

Publications

Virus-like Nonvirus Cationic Liposome for Efficient Gene Delivery via Endoplasmic Reticulum Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets