scholarly journals Aminoglycosides: From Antibiotics to Building Blocks for the Synthesis and Development of Gene Delivery Vehicles

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 504 ◽  
Author(s):  
Maria Cristina Bellucci ◽  
Alessandro Volonterio
Keyword(s):  
Gene Delivery ◽  
Bacterial Infections ◽  
Genetic Material ◽  
Building Blocks ◽  
Cationic Lipids ◽  
Naturally Occurring ◽  
Long Time ◽  
Delivery Vehicles ◽  
Polymeric Vectors ◽  
Acquired Antibiotic Resistance

Aminoglycosides are a class of naturally occurring and semi synthetic antibiotics that have been used for a long time in fighting bacterial infections. Due to acquired antibiotic resistance and inherent toxicity, aminoglycosides have experienced a decrease in interest over time. However, in the last decade, we are seeing a renaissance of aminoglycosides thanks to a better understanding of their chemistry and mode of action, which had led to new trends of application. The purpose of this comprehensive review is to highlight one of these new fields of application: the use of aminoglycosides as building blocks for the development of liposomal and polymeric vectors for gene delivery. The design, synthetic strategies, ability to condensate the genetic material, the efficiency in transfection, and cytotoxicity as well as when available, the antibacterial activity of aminoglycoside-based cationic lipids and polymers are covered and critically analyzed.

Degradable Dextran Particles for Gene Delivery Applications

2012 ◽  
Vol 65 (1) ◽  
pp. 15 ◽  
Author(s):  
Peter R. Wich ◽  
Jean M. J. Fréchet
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Genetic Material ◽  
Short Review ◽  
Viral Gene ◽  
Target Cells ◽  
Triggered Release ◽  
Delivery Vehicles ◽  
Safe Transport ◽  
Particulate Delivery

Successful gene therapy depends both on the effective transport and the stable expression of therapeutic genes to produce and regulate disease related proteins. In this context, non-viral gene delivery vehicles are regarded as one of the most promising approaches for the efficient and safe transport of genetic material to and into the target cells. This short review describes the development of novel particulate delivery vehicles based on the biopolymer dextran. This multifunctional platform was designed to safely transport genetic material across cell membranes, followed by an acid triggered release that causes overall high transfection efficiency. The biocompatibility and its unique tunability differentiate this new carrier system from previous particle systems, showing high potential for the treatment of several disease models in RNA interference related applications.

scholarly journals Gene Therapy: Design and Prospects for Craniofacial Regeneration

2009 ◽  
Vol 88 (7) ◽  
pp. 585-596 ◽  
Author(s):  
E.L. Scheller ◽  
P.H. Krebsbach
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Genetic Material ◽  
Building Blocks ◽  
Tissue Growth ◽  
Viral Gene ◽  
Insert Size ◽  
Relative Safety ◽  
Size Limitation

Gene therapy is defined as the treatment of disease by transfer of genetic material into cells. This review will explore methods available for gene transfer as well as current and potential applications for craniofacial regeneration, with emphasis on future development and design. Though non-viral gene delivery methods are limited by low gene transfer efficiency, they benefit from relative safety, low immunogenicity, ease of manufacture, and lack of DNA insert size limitation. In contrast, viral vectors are nature’s gene delivery machines that can be optimized to allow for tissue-specific targeting, site-specific chromosomal integration, and efficient long-term infection of dividing and non-dividing cells. In contrast to traditional replacement gene therapy, craniofacial regeneration seeks to use genetic vectors as supplemental building blocks for tissue growth and repair. Synergistic combination of viral gene therapy with craniofacial tissue engineering will significantly enhance our ability to repair and replace tissues in vivo.

α-Tocopherol-anchored gemini lipids with delocalizable cationic head groups: Effect of spacer length on DNA compaction and transfection properties

2021 ◽  
Author(s):  
Mallikarjun Gosangi ◽  
Venkatesh Ravula ◽  
Hithavani Rapaka ◽  
Srilakshmi V Patri
Keyword(s):  
Gene Delivery ◽  
Cationic Lipids ◽  
Spacer Length ◽  
Dna Compaction ◽  
Structure Activity ◽  
Head Groups ◽  
Efficient Gene ◽  
Delivery Vehicles ◽  
Systematic Structure

Understanding the role of structural units in cationic lipids used for gene delivery is essential in designing efficient gene delivery vehicles. Herein we report a systematic structure-activity investigation on the...

scholarly journals Crossing the Blood-Brain-Barrier: A bifunctional liposome for BDNF gene delivery – A Pilot Study

2020 ◽  
Author(s):  
Danielle M. Diniz ◽  
Silvia Franze ◽  
Judith R. Homberg
Keyword(s):  
Pilot Study ◽  
Gene Delivery ◽  
Blood Brain Barrier ◽  
Genetic Material ◽  
Physicochemical Characterization ◽  
Cationic Lipids ◽  
Brain Barrier ◽  
Blood Brain ◽  
Loading Efficiency ◽  
The Brain

AbstractTo achieve their therapeutic effect on the brain, molecules need to pass the blood-brain-barrier (BBB). Many pharmacological treatments of neuropathologies encounter the BBB as a barrier, hindering their effective use. Pharmaceutical nanotechnology based on optimal physicochemical features and taking advantage of naturally occurring permeability mechanisms, nanocarriers such as liposomes offer an attractive alternative to allow drug delivery across the BBB. Liposomes are spherical bilayer lipid-based nanocapsules that can load hydrophilic molecules in their inner compartment and on their outer surface can be functionally modified by peptides, antibodies and polyethyleneglycol (PEG). When composed of cationic lipids, liposomes can serve as gene delivery devices, encapsulating and protecting genetic material from degradation and promoting nonviral cell transfection. In this study, we aimed to develop a liposomal formulation to encapsulate a plasmid harbouring brain-derived neurotrophic factor (BDNF) and infuse these liposomes via the peripheral bloodstream into the brain. To this end, liposomes were tagged with PEG, transferrin, and arginine and characterized regarding their physical properties, such as particle size, zeta-potential and polydispersity index (PDI). Moreover, we selected liposomes preparations for plasmid DNA (pDNA) encapsulation and checked for loading efficiency, in vitro cell uptake, and transfection. The preliminary results from this pilot study revealed that we were able to replicate the liposomes synthesis described in literature, achieving compatible size, charge, PDI, and loading efficiency. However, we could not properly determine whether the conjugation of the surface ligands transferrin and arginine to PEG worked and whether they were attached to the surface of the liposomes. Additionally, we were not able to see transfection in SH-SY5Y cells after 24 or 48 hours of incubation with the pDNA loaded liposomes. In conclusion, we synthesized liposomes encapsulation pBDNF, however, further research will be necessary to address the complete physicochemical characterization of the liposomes. Furthermore, preclinical studies will be helpful to verify transfection efficiency, cytotoxicity, and in the future, safe delivery of BDNF through the BBB.

scholarly journals Pulmonary gene delivery—Realities and possibilities

2020 ◽  
pp. 153537022096598
Author(s):  
Uday K Baliga ◽  
David A Dean
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Extracellular Vesicles ◽  
Viral Vectors ◽  
Neutral Lipids ◽  
Genetic Material ◽  
Building Blocks ◽  
Electrical Pulses ◽  
Primary Focus

Delivery of genetic material to tissues in vivo is an important technique used in research settings and is the foundation upon which clinical gene therapy is built. The lung is a prime target for gene delivery due to a host of genetic, acquired, and infectious diseases that manifest themselves there, resulting in many pathologies. However, the in vivo delivery of genetic material to the lung remains a practical problem clinically and is considered the major obstacle needed to be overcome for gene therapy. Currently there are four main strategies for in vivo gene delivery to the lung: viral vectors, liposomes, nanoparticles, and electroporation. Viral delivery uses several different genetically modified viruses that enter the cell and express desired genes that have been inserted to the viral genome. Liposomes use combinations of charged and neutral lipids that can encapsulate genetic cargo and enter cells through endogenous mechanisms, thereby delivering their cargoes. Nanoparticles are defined by their size (typically less than 100 nm) and are made up of many different classes of building blocks, including biological and synthetic polymers, cell penetrant and other peptides, and dendrimers, that also enter cells through endogenous mechanisms. Electroporation uses mild to moderate electrical pulses to create pores in the cell membrane through which delivered genetic material can enter a cell. An emerging fifth category, exosomes and extracellular vesicles, may have advantages of both viral and non-viral approaches. These extracellular vesicles bud from cellular membranes containing receptors and ligands that may aid cell targeting and which can be loaded with genetic material for efficient transfer. Each of these vectors can be used for different gene delivery applications based on mechanisms of action, side-effects, and other factors, and their use in the lung and possible clinical considerations is the primary focus of this review.

Stepwise Development of Biomimetic Chimeric Peptides for Gene Delivery

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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