Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes

Background: Mesenchymal stem cells (MSCs) are stem cells present in adult tissues. They can be cultured, have great growth capacity, and can differentiate into several cell types. The isolation of urine-derived mesenchymal stem cells (hUSCs) was recently described. hUSCs present additional benefits in the fact that they can be easily obtained noninvasively. Regarding gene delivery, nonviral vectors based on cationic niosomes have been used and are more stable and have lower immunogenicity than viral vectors. However, their transfection efficiency is low and in need of improvement. Methods: We isolated hUSCs from urine, and the cell culture was tested and characterized. Different cationic niosomes were elaborated using reverse-phase evaporation, and they were physicochemically characterized. Then, they were screened into hUSCs for transfection efficiency, and their internalization was evaluated. Results: GPxT-CQ at a lipid/DNA ratio of 5:1 (w/w) had the best transfection efficiency. Intracellular localization studies confirmed that nioplexes entered mainly via caveolae-mediated endocytosis. Conclusions: In conclusion, we established a protocol for hUSC isolation and their transfection with cationic niosomes, which could have relevant clinical applications such as in gene therapy. This methodology could also be used for creating cellular models for studying and validating pathogenic genetic variants, and even for performing functional studies. Our study increases knowledge about the internalization of tested cationic niosomes in these previously unexplored cells.

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WITHDRAWN: Non-viral vectors based on cationic niosomes as efficient gene delivery vehicles to central nervous system cells into the brain

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2018.05.057 ◽

2018 ◽

Author(s):

Mohamed Mashal ◽

Noha Attia ◽

Cristina Soto-Sánchez ◽

Gema Martínez-Navarrete ◽

Eduardo Fernández ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Gene Delivery ◽

Viral Vectors ◽

Efficient Gene ◽

Delivery Vehicles ◽

The Brain ◽

Cationic Niosomes ◽

Gene Delivery Vehicles

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Non-viral vectors based on cationic niosomes as efficient gene delivery vehicles to central nervous system cells into the brain

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2018.09.038 ◽

2018 ◽

Vol 552 (1-2) ◽

pp. 48-55 ◽

Cited By ~ 11

Author(s):

Mohamed Mashal ◽

Noha Attia ◽

Cristina Soto-Sánchez ◽

Gema Martínez-Navarrete ◽

Eduardo Fernández ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Gene Delivery ◽

Viral Vectors ◽

Efficient Gene ◽

Delivery Vehicles ◽

The Brain ◽

Cationic Niosomes ◽

Gene Delivery Vehicles

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Gene Delivery using Non-Viral Vectors (Cyclodextrins) with Pluronic-F127 and Folic Acid

10.3390/ecps2012-00798 ◽

2012 ◽

Author(s):

Matthew Eng ◽

Amal Elkordy

Keyword(s):

Folic Acid ◽

Gene Delivery ◽

Viral Vectors ◽

Pluronic F127

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Polyplex: A Promising Gene Delivery System

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285//ijpsn.2019.12.6.1 ◽

2019 ◽

Vol 12 (6) ◽

pp. 4681-4686

Author(s):

Rohan Aggarwal ◽

Monika Targhotra ◽

Bhumika Kumar ◽

P.K Sahoo ◽

Meenakshi K Chauhan

Keyword(s):

Gene Transfer ◽

Gene Delivery ◽

Delivery System ◽

Viral Vectors ◽

Gene Delivery System ◽

Cationic Polymers ◽

Therapeutic Application ◽

Promising Alternative ◽

Structure And Stability ◽

The Past

In the past few years gene delivery system has gained a huge attention owing to its proved efficacy in several diseases especially in those caused by genetic and/oroncological malfunctioning. The effective gene delivery mainly depends on the carrier molecules that can ensure the safe and specific delivery of the nucleic acidmolecules. Viral vectors have been used for a longer period as the gene transfer vehicle. However, these viral vectors have potential immunological disadvantages that made them less preferred. Recently, non-viral vectors such as polyplexes have emerged as a promising alternative for viral vectors. Polyplexes are formed by conjugating a polymer with DNA and in maximum cases the cationic polymers are preferred over others. The structure and stability of the polyplexes depends on various factors. The ability of the polymer to condense the DNA mainly dictates the efficiency of the polyplex mediated transfection. In this review we are going to provide a framework for the synthesis and design of the polyplexes along with the structure and stability of the complexes pertaining to mechanism of action, characterization and therapeutic application, including polyethyleneimine mediated cytotoxicity as well as newer strategies for the generation of better polyplexes.

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Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

Protein and Peptide Letters ◽

10.2174/0929866527666200206153328 ◽

2020 ◽

Vol 27 (8) ◽

pp. 698-710

Author(s):

Roya Cheraghi ◽

Mahboobeh Nazari ◽

Mohsen Alipour ◽

Saman Hosseinkhani

Keyword(s):

Gene Delivery ◽

Targeted Delivery ◽

Viral Vectors ◽

Large Scale ◽

Transfection Efficiency ◽

Cationic Lipids ◽

Target Cells ◽

Scale Production ◽

Stepwise Development ◽

Chimeric Peptides

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.

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Physical Characterisation as an Insight into a Gene Delivery System Containing Cyclodextrins with Pluronic®-F127 and Folic acid as Non-Viral Vectors

Current Pharmaceutical Biotechnology ◽

10.2174/1389201015666140827102134 ◽

2014 ◽

Vol 15 (8) ◽

pp. 712-726

Author(s):

Matthew Eng ◽

Amal Elkordy ◽

Paul McCarron ◽

Eman Elkordy ◽

Ahmed Faheem

Keyword(s):

Folic Acid ◽

Gene Delivery ◽

Delivery System ◽

Viral Vectors ◽

Gene Delivery System ◽

Insight Into

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Systemic AAV6-synapsin-GFP administration results in lower liver biodistribution, compared to AAV1&2 and AAV9, with neuronal expression following ultrasound-mediated brain delivery

Scientific Reports ◽

10.1038/s41598-021-81046-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Danielle Weber-Adrian ◽

Rikke Hahn Kofoed ◽

Joseph Silburt ◽

Zeinab Noroozian ◽

Kairavi Shah ◽

...

Keyword(s):

Gene Delivery ◽

Intravenous Injection ◽

Viral Vectors ◽

Focused Ultrasound ◽

Fluorescent Protein ◽

Gfp Expression ◽

Peripheral Organs ◽

Neuronal Expression ◽

Green Fluorescent ◽

The Brain

AbstractNon-surgical gene delivery to the brain can be achieved following intravenous injection of viral vectors coupled with transcranial MRI-guided focused ultrasound (MRIgFUS) to temporarily and locally permeabilize the blood–brain barrier. Vector and promoter selection can provide neuronal expression in the brain, while limiting biodistribution and expression in peripheral organs. To date, the biodistribution of adeno-associated viruses (AAVs) within peripheral organs had not been quantified following intravenous injection and MRIgFUS delivery to the brain. We evaluated the quantity of viral DNA from the serotypes AAV9, AAV6, and a mosaic AAV1&2, expressing green fluorescent protein (GFP) under the neuron-specific synapsin promoter (syn). AAVs were administered intravenously during MRIgFUS targeting to the striatum and hippocampus in mice. The syn promoter led to undetectable levels of GFP expression in peripheral organs. In the liver, the biodistribution of AAV9 and AAV1&2 was 12.9- and 4.4-fold higher, respectively, compared to AAV6. The percentage of GFP-positive neurons in the FUS-targeted areas of the brain was comparable for AAV6-syn-GFP and AAV1&2-syn-GFP. In summary, MRIgFUS-mediated gene delivery with AAV6-syn-GFP had lower off-target biodistribution in the liver compared to AAV9 and AAV1&2, while providing neuronal GFP expression in the striatum and hippocampus.

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How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

International Journal of Molecular Sciences ◽

10.3390/ijms22147545 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7545

Author(s):

Myriam Sainz-Ramos ◽

Idoia Gallego ◽

Ilia Villate-Beitia ◽

Jon Zarate ◽

Iván Maldonado ◽

...

Keyword(s):

Gene Therapy ◽

Clinical Practice ◽

Gene Delivery ◽

Viral Vectors ◽

Viral Vector ◽

Clinical Success ◽

Genetic Material ◽

Viral Gene ◽

Promising Alternative ◽

Vector Systems

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

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