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Polycation gene delivery systems: escape from endosomes to cytosol

Identifieur interne : 002074 ( Main/Exploration ); précédent : 002073; suivant : 002075

Polycation gene delivery systems: escape from endosomes to cytosol

Auteurs : Yong Woo Cho [États-Unis] ; Jong-Duk Kim [Corée du Sud] ; Kinam Park [États-Unis]

Source :

RBID : ISTEX:BFD02E76363884EF5A6923B1ABA4610BCB8655EF

English descriptors

Abstract

Clinical success of gene therapy based on oligonucleotides (ODNs), ribozymes, RNA and DNA will be greatly dependent on the availability of effective delivery systems. Polycations have gained increasing attention as a non‐viral gene delivery vector in the past decades. Significant progress has been made in understanding complex formation between polycations and nucleic acids, entry of the complex into the cells and subsequent entry into the nucleus. Sophisticated molecular architectures of cationic polymers have made the vectors more stable and less susceptible to binding by enzymes or proteins. Incorporation of specific ligands to polycations has resulted in more cell‐specific uptake by receptor‐mediated mechanisms. However, there are still other barriers limiting the transfection efficiency of polycation gene delivery systems. There is a consensus that polycation‐DNA complexes (polyplexes) enter cells via the endocytotic pathway. It is not clearly understood, however, how the polyplexes escape (if they do) from endosomes, how DNA is released from the polyplexes or how the released DNA is expressed. The primary focus of this article is to review various polycation gene delivery systems, which are designed to translocate DNA from endosomes into cytosol. Many polycation gene delivery systems have tried to mimic the mechanisms that viruses use for the endosomal escape. Polycation gene delivery systems are usually coupled with synthetic amphipathic peptides mimicking viral fusogenic peptides, histidine‐based gene delivery systems for pH‐responsive endosomal escape, polycations with intrinsic endosomolytic activity by the proton sponge mechanism and polyanions to mimic the anionic amphiphilic peptides.

Url:
DOI: 10.1211/002235703765951311


Affiliations:


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Le document en format XML

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<term>Acad</term>
<term>Acidic</term>
<term>Acidic environment</term>
<term>Acidic medium</term>
<term>Acrylic acid</term>
<term>Adenovirus</term>
<term>Adenovirus particles</term>
<term>Amino</term>
<term>Amino groups</term>
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<term>Cationic</term>
<term>Charge ratio</term>
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<term>Chemical structure</term>
<term>Chloroquine</term>
<term>Complex formation</term>
<term>Complex nanoparticles</term>
<term>Complex particles</term>
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<term>Conformational change</term>
<term>Copolymer</term>
<term>Cytosol</term>
<term>Dendrimers</term>
<term>Efficient gene transfer</term>
<term>Endocytosis</term>
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<term>Endosomal membrane</term>
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<term>Fusogenic peptide</term>
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<term>Gene delivery</term>
<term>Gene delivery systems</term>
<term>Gene expression</term>
<term>Gene transfer</term>
<term>Haemolytic activity</term>
<term>Haensler szoka</term>
<term>Helical</term>
<term>Helical conformation</term>
<term>Helical content</term>
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<term>High transfection efficiency</term>
<term>Histidine</term>
<term>Histidine residues</term>
<term>Histidyl</term>
<term>Histidyl residues</term>
<term>Histidylated</term>
<term>Histidylated oligolysine</term>
<term>Histidylated oligolysines</term>
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<term>Lipid bilayers</term>
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<term>Lysine residues</term>
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<term>Odns</term>
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<div type="abstract" xml:lang="en">Clinical success of gene therapy based on oligonucleotides (ODNs), ribozymes, RNA and DNA will be greatly dependent on the availability of effective delivery systems. Polycations have gained increasing attention as a non‐viral gene delivery vector in the past decades. Significant progress has been made in understanding complex formation between polycations and nucleic acids, entry of the complex into the cells and subsequent entry into the nucleus. Sophisticated molecular architectures of cationic polymers have made the vectors more stable and less susceptible to binding by enzymes or proteins. Incorporation of specific ligands to polycations has resulted in more cell‐specific uptake by receptor‐mediated mechanisms. However, there are still other barriers limiting the transfection efficiency of polycation gene delivery systems. There is a consensus that polycation‐DNA complexes (polyplexes) enter cells via the endocytotic pathway. It is not clearly understood, however, how the polyplexes escape (if they do) from endosomes, how DNA is released from the polyplexes or how the released DNA is expressed. The primary focus of this article is to review various polycation gene delivery systems, which are designed to translocate DNA from endosomes into cytosol. Many polycation gene delivery systems have tried to mimic the mechanisms that viruses use for the endosomal escape. Polycation gene delivery systems are usually coupled with synthetic amphipathic peptides mimicking viral fusogenic peptides, histidine‐based gene delivery systems for pH‐responsive endosomal escape, polycations with intrinsic endosomolytic activity by the proton sponge mechanism and polyanions to mimic the anionic amphiphilic peptides.</div>
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