scholarly journals Retinal Multipotent Stem-Cell Derived “MiEye” Spheroid 3D Culture Model for Preclinical Screening of Non-viral Gene Delivery Systems

2018 ◽  
Vol 1 (2) ◽  
pp. 106-123 ◽  
Author(s):  
Ding-Wen Chen ◽  
Marianna Foldvari
Keyword(s):  
Stem Cell ◽  
Gene Delivery ◽  
3D Culture ◽  
Viral Gene ◽  
Microscopy Imaging ◽  
Multipotent Stem Cell ◽  
Promising Therapeutic Approach ◽  
Culture Model ◽  
Preclinical Screening

Non-viral retinal gene therapy is a promising therapeutic approach towards the management of retinal degenerative diseases especially glaucoma. Current methods of in vitro preclinical screening of candidate nanoparticle systems in monolayer cell cultures are not reliable in predicting in vivo performance. In this paper, we describe the development of a multipotent stem-cell derived three-dimensional “mini-retina” culture model (MiEye) that aims to simulate an in vivo clinical model for more reliable gene delivery system screening. Through the utilization of multiplex gene expression profiling, we have shown that retinal stem cells can be differentiated in 3D culture to generate retinal neurospheres comprising of multiple retinal cell types. The 3D cell culture model combined with confocal microscopy imaging and fluorescence profiling techniques is a powerful tool as a retinal gene and drug delivery screening model.

scholarly journals In vivo gene delivery by embryonic-stem-cell–derived astrocytes for malignant gliomas

2009 ◽  
Vol 11 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Mahmud Uzzaman ◽  
Gordon Keller ◽  
Isabelle M. Germano
Keyword(s):  
Stem Cell ◽  
Gene Delivery ◽  
Embryonic Stem Cell ◽  
Malignant Gliomas ◽  
Embryonic Stem ◽  
In Vivo Gene Delivery

scholarly journals Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1964
Author(s):  
Huaiying Zhang ◽  
Damla Keskin ◽  
Willy H. de Haan-Visser ◽  
Guangyue Zu ◽  
Patrick van Rijn ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Tertiary Amine ◽  
Quaternary Ammonium ◽  
Gene Transfection ◽  
Genetic Material ◽  
Cationic Lipid ◽  
Endosomal Escape ◽  
Hereditary Diseases ◽  
Viral Gene

Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(N-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.

scholarly journals A ligand-based system for receptor-specific delivery of proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mariano Maffei ◽  
Chiara Morelli ◽  
Ellie Graham ◽  
Stefano Patriarca ◽  
Laura Donzelli ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Protein Delivery ◽  
Genetic Diseases ◽  
Cell Surface Receptor ◽  
Viral Gene ◽  
Promising Alternative ◽  
Large Proteins ◽  
Reporter Mice ◽  
Surface Receptor

AbstractGene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand’s cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases.

Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 342-343 ◽  
pp. 449-452 ◽  
Author(s):  
Tae Hee Kim ◽  
Hua Jin ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

Gene-Eluting Stents: Comparison of Adenoviral and Adeno- Associated Viral Gene Delivery to the Blood Vessel Wall In Vivo

2006 ◽  
Vol 17 (7) ◽  
pp. 741-750 ◽  
Author(s):  
Faisal Sharif ◽  
Sean O. Hynes ◽  
Jill McMahon ◽  
Ronan Cooney ◽  
Siobhan Conroy ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Blood Vessel ◽  
Vessel Wall ◽  
Viral Gene ◽  
Blood Vessel Wall ◽  
Viral Gene Delivery

scholarly journals Dual non-viral gene delivery from microparticles within 3D high-density stem cell constructs for enhanced bone tissue engineering

Biomaterials ◽  
2018 ◽  
Vol 161 ◽  
pp. 240-255 ◽  
Author(s):  
Alexandra McMillan ◽  
Minh Khanh Nguyen ◽  
Tomas Gonzalez-Fernandez ◽  
Peilin Ge ◽  
Xiaohua Yu ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Gene Delivery ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
High Density ◽  
Viral Gene ◽  
Viral Gene Delivery
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