Cell Biological and Biophysical Aspects of Lipid-mediated Gene Delivery

2006 ◽  
Vol 26 (4) ◽  
pp. 301-324 ◽  
Author(s):  
N. Madhusudhana Rao ◽  
Vijaya Gopal
Keyword(s):  
Gene Delivery ◽  
Viral Vectors ◽  
First Generation ◽  
Cationic Lipid ◽  
Cationic Lipids ◽  
Biological Knowledge ◽  
Effective Strategies ◽  
Hydrophilic Region

Cationic lipids are conceptually and methodologically simple tools to deliver nucleic acids into the cells. Strategies based on cationic lipids are viable alternatives to viral vectors and are becoming increasingly popular owing to their minimal toxicity. The first-generation cationic lipids were built around the quaternary nitrogen primarily for binding and condensing DNA. A large number of lipids with variations in the hydrophobic and hydrophilic region were generated with excellent transfection efficiencies in vitro. These cationic lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in the last decade delineated the cell biological basis of the cationic lipid gene delivery to a significant detail. The application of techniques such as small angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking the physical properties of lipid:DNA complex (lipoplex) with its intracellular fate. This biological knowledge has been incorporated in the design of the second-generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective strategies to overcome the various cellular barriers along with the lipoplex formulations methodologies. In this context, cationic lipid-mediated gene delivery is considerably benefited by the methodologies of liposome-mediated drug delivery. Lipid mediated gene delivery has an intrinsic advantage of being a biomimetic platform on which considerable variations could be built to develop efficient in vivo gene delivery protocols.

scholarly journals Tri-peptide cationic lipids for gene delivery

2015 ◽  
Vol 3 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Yinan Zhao ◽  
Shubiao Zhang ◽  
Yuan Zhang ◽  
Shaohui Cui ◽  
Huiying Chen ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Tumor Cells ◽  
Cationic Lipid ◽  
Cationic Lipids

A novel tri-peptide cationic lipid can efficiently transfer DNA and siRNA into tumor cells and tumors of mice with little in vitro and in vivo toxicity.

scholarly journals Selective Anti-melanoma Effect of Phosphothioated Aptamer Encapsulated by Neutral Cytidinyl/Cationic Lipids

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Wu ◽  
Shuhe Wang ◽  
Xiang Li ◽  
Qi Zhang ◽  
Jie Yang ◽  
...  
Keyword(s):  
Cationic Lipid ◽  
Cationic Lipids ◽  
Dna Aptamer ◽  
Cell Permeability ◽  
Hnrnp A1 ◽  
New Strategy ◽  
Rna Maturation ◽  
Nuclear Ribonucleoprotein

BC15-31 is a DNA aptamer that targets heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which plays a crucial role in the process of pre-RNA maturation and is also essential for the rapid proliferation of tumor cells. In this research, we modified BC15-31 with a phosphorothioate (PS) backbone, LNA, and 2-O-MOE to enhance its stability and target affinity. In addition, a neutral cytidinyl lipid (DNCA) and a cationic lipid (CLD) were mixed to encapsulate modified aptamers with the aim of improving their cell permeability with low toxicity. Under the DNCA/CLD package, aptamers are mainly distributed in the nucleus. A modified sequence WW-24 showed an excellent selective anti-melanoma (A375 cells, ∼25 nM, 80%) activity, targeted to both hnRNP A1 and hnRNP A2/B1 found by the BLI experiment, and induced more early and late apoptosis in vitro, which also showed stronger antitumor effect and longer accumulation time in vivo. These results provide a new strategy for further clinical applications.

scholarly journals Scaffold-Mediated Gene Delivery for Osteochondral Repair

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 930 ◽  
Author(s):  
Henning Madry ◽  
Jagadeesh Kumar Venkatesan ◽  
Natalia Carballo-Pedrares ◽  
Ana Rey-Rico ◽  
Magali Cucchiarini
Keyword(s):  
Gene Delivery ◽  
Viral Vectors ◽  
Viral Gene ◽  
Therapeutic Gene ◽  
Therapeutic Concept ◽  
Osteochondral Repair ◽  
Gene Vectors ◽  
A Site

Osteochondral defects involve both the articular cartilage and the underlying subchondral bone. If left untreated, they may lead to osteoarthritis. Advanced biomaterial-guided delivery of gene vectors has recently emerged as an attractive therapeutic concept for osteochondral repair. The goal of this review is to provide an overview of the variety of biomaterials employed as nonviral or viral gene carriers for osteochondral repair approaches both in vitro and in vivo, including hydrogels, solid scaffolds, and hybrid materials. The data show that a site-specific delivery of therapeutic gene vectors in the context of acellular or cellular strategies allows for a spatial and temporal control of osteochondral neotissue composition in vitro. In vivo, implantation of acellular hydrogels loaded with nonviral or viral vectors has been reported to significantly improve osteochondral repair in translational defect models. These advances support the concept of scaffold-mediated gene delivery for osteochondral repair.

Functional Amphiphiles for Gene Delivery

MRS Bulletin ◽  
2005 ◽  
Vol 30 (9) ◽  
pp. 647-653 ◽  
Author(s):  
Philippe Barthélémy ◽  
Michel Camplo
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Research Activity ◽  
Safety Issues ◽  
Significant Research

AbstractThe design of safe and efficient gene transfer vectors remains one of the key challenges in gene therapy. Despite their remarkable transfection efficiency, viral vectors suffer from known safety issues. Consequently, significant research activity has been undertaken to develop nonviral approaches to gene transfer during the last decade. Numerous academic and industrial research groups are investigating synthetic cationic vectors, such as cationic amphiphiles, with the objective of increasing the gene transfection activity. Within this area, the development of functional synthetic vectors that respond to local environmental effects have met with success. These synthetic vectors are based on mechanistic principles and represent a significant departure from earlier systems. Many of these systems for gene delivery in vitro and in vivo are discussed in this article.

scholarly journals Gemini Cationic Lipid-Type Nanovectors Suitable for the Transfection of Therapeutic Plasmid DNA Encoding for Pro-Inflammatory Cytokine Interleukin-12

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 729
Author(s):  
Natalia Sánchez-Arribas ◽  
María Martínez-Negro ◽  
Clara Aicart-Ramos ◽  
Conchita Tros de Ilarduya ◽  
Emilio Aicart ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Physicochemical Characterization ◽  
Cationic Lipid ◽  
Cationic Lipids ◽  
Interleukin 12 ◽  
Dna Encoding ◽  
Lipid Mixture ◽  
Ample Evidence

Ample evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.

Replacement of quaternary ammonium headgroups by tri-ornithine in cationic lipids for the improvement of gene delivery in vitro and in vivo

2017 ◽  
Vol 5 (39) ◽  
pp. 7963-7973 ◽  
Author(s):  
Y. N. Zhao ◽  
Y. Z. Piao ◽  
C. M. Zhang ◽  
Y. M. Jiang ◽  
A. Liu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Quaternary Ammonium ◽  
Cationic Lipids

Replacement of quaternary ammonium headgroups by tri-ornithine in lipids improved gene delivery in vitro and in vivo with little toxicity.

Synthesis of α-amino-lipophosphonates as cationic lipids or co-lipids for DNA transfection in dendritic cells

2017 ◽  
Vol 5 (33) ◽  
pp. 6869-6881 ◽  
Author(s):  
Mathieu Berchel ◽  
Sohail Akhter ◽  
Wilfried Berthe ◽  
Cristine Gonçalves ◽  
Marine Dubuisson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Cationic Lipid ◽  
Cationic Lipids ◽  
Dna Transfection

Cationic lipid/co-lipid combinations have been extensively explored in gene delivery as alternatives to viral vectors.

Hyaluronic acid–PEI–cyclodextrin polyplexes: implications for in vitro and in vivo transfection efficiency and toxicity

RSC Advances ◽  
2015 ◽  
Vol 5 (51) ◽  
pp. 41144-41154 ◽  
Author(s):  
S. Jain ◽  
S. Kumar ◽  
A. K. Agrawal ◽  
K. Thanki ◽  
U. C. Banerjee
Keyword(s):  
Hyaluronic Acid ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
In Vivo Transfection

The present study reveals novel HA–PEI–CyD polyplexes as non-viral vectors for gene delivery.

scholarly journals Silica-Based Gene Delivery Systems: From Design to Therapeutic Applications

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 649 ◽  
Author(s):  
Ana Maria Carvalho ◽  
Rosemeyre A. Cordeiro ◽  
Henrique Faneca
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Genetic Material ◽  
Successful Outcome ◽  
Inorganic Particles ◽  
Therapeutic Applications

Advances in gene therapy have been foreshadowing its potential for the treatment of a vast range of diseases involving genetic malfunctioning. However, its therapeutic efficiency and successful outcome are highly dependent on the development of the ideal gene delivery system. On that matter, silica-based vectors have diverted some attention from viral and other types of non-viral vectors due to their increased safety, easily modifiable structure and surface, high stability, and cost-effectiveness. The versatility of silane chemistry and the combination of silica with other materials, such as polymers, lipids, or inorganic particles, has resulted in the development of carriers with great loading capacities, ability to effectively protect and bind genetic material, targeted delivery, and stimuli-responsive release of cargos. Promising results have been obtained both in vitro and in vivo using these nanosystems as multifunctional platforms in different potential therapeutic areas, such as cancer or brain therapies, sometimes combined with imaging functions. Herein, the current advances in silica-based systems designed for gene therapy are reviewed, including their main properties, fabrication methods, surface modifications, and potential therapeutic applications.

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