“Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years”

Crowley, Samuel T.; Rice, Kevin G.

doi:10.1016/j.jconrel.2015.10.008

Cited by 10 publications

(6 citation statements)

References 254 publications

(300 reference statements)

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“…The major limiting factor of nonviral gene delivery systems is the efficient cytosolic diffusion and the nuclear entry of the plasmid DNA (pDNA) [19,20], but unlike pDNA, mRNA does not require delivery into the cell nucleus as translation occurs in the cytosol [19,21]. Moreover, mRNA does not integrate into the genomic DNA [19,22].…”

Section: Introductionmentioning

confidence: 99%

Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells

Choi

Lee

Yang

et al. 2016

Journal of Controlled Release

100

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Section: Introductionmentioning

confidence: 99%

Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells

Choi

Lee

Yang

et al. 2016

Journal of Controlled Release

100

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“…■ MAG AND GalNAc BLOCK COPOLYMERS: ENHANCED COLLOIDAL STABILITY AND TISSUE TARGETING Although the PGAA system yielded efficient and nontoxic delivery of nucleic acid acids both in vitro and in vivo, systemic injection into an organism ultimately requires colloidally stable complexes less than 100 nm in size that resist aggregation in the presence of salt and serum while maintaining efficacy. 31 Many polycations, such as PEI, form large aggregates that are quickly cleared from the body by the reticuloendothelial system and can also be caught in lung capillaries. 3 A common strategy to increase the colloidal stability of polyplexes is to prepare diblock copolymer architectures composed of both a cationic block, such as N-(2-aminoethyl) methacrylamide (AEMA), and a hydrophilic block, such as poly(ethylene glycol) (PEG).…”

Section: ■ Intracellular Trafficking Of Pgaasmentioning

confidence: 99%

Nonviral Gene Delivery with Cationic Glycopolymers

et al. 2019

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Conspectus The field of gene therapy, which aims to treat patients by modulating gene expression, has come to fruition and has landed several landmark FDA approvals. Most gene therapies currently rely on viral vectors to deliver nucleic acid cargo into cells, but there is significant interest in moving toward chemical-based methods, such as polymer-based vectors, due to their low cost, immunocompatibility, and tunability. The full potential of polymer-based delivery systems has yet to be realized, however, because most polymeric transfection reagents are either too inefficient or too toxic for use in the clinic. In this Account, we describe developments in carbohydrate-based cationic polymers, termed glycopolymers, for enhanced nonviral gene delivery. As ubiquitous components of biological systems, carbohydrates are a rich class of compounds that can be harnessed to improve the biocompatibility of non-native polymers, such as linear polyamines used for promoting transfection. Reineke et al. developed a new class of carbohydrate-based polymers called poly(glycoamidoamine)s (PGAAs) by step-growth polymerization of linear monosaccharides with linear ethyleneamines. These glycopolymers were shown to be both efficient and biocompatible transfection reagents. Systematic modifications of the structural components of the PGAA system revealed structure–activity relationships important to its function, including its ability to degrade in situ. Expanding upon the development of step-growth glycopolymers, monosaccharides, such as glucose, were functionalized as vinyl-based monomers for the formation of diblock copolymers via radical addition–fragmentation chain-transfer (RAFT) polymerization. Upon complexation with plasmid DNA, the glucose-containing block creates a hydrophilic shell that promotes colloidal stability as effectively as PEG functionalization. An N-acetyl-d-galactosamine variant of this diblock polymer yields colloidally stable particles that show increased receptor-mediated uptake by liver hepatocytes in vitro and promotes liver targeting in mice. Finally, the disaccharide trehalose was incorporated into polycationic structures using both step-growth and RAFT techniques. It was shown that these trehalose-based copolymers imparted increased colloidal stability and yielded plasmid and siRNA polyplexes that resist aggregation upon lyophilization and reconstitution in water. The aforementioned series of glycopolymers use carbohydrates to promote effective and safe delivery of nucleic acid cargo into a variety of human cells types by promoting vehicle degradation, tissue-targeting, colloidal stabilization, and stability toward lyophilization to extend shelf life. Work is currently underway to translate the use of glycopolymers for safe and efficient delivery of nucleic acid cargo for gene therapy and gene editing applications.

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“…Mitochondria possess their own genome, mitochondrial DNA (mtDNA), with a gene expression system that is independent of the nuclear system, and regulate cellular functions in cooperation with the nucleus [1]. To date, many useful technologies regarding nuclear transgene expression have been reported [2][3][4][5], and a wide variety of plasmid DNA (pDNA) vectors have been developed and are now used as convenient and useful tools for transgene expression by many researchers and clinicians world-wide [5]. It is well known that mitochondria possess their own transcription/translation system and a unique codon usage that is different from universal codon usage.…”

Section: Introductionmentioning

confidence: 99%

“…Collectively, the KALA-MITO-Porter was efficiently internalized by the cells, and delivered large amounts of the pCMV-mtLuc (CGG) to mitochondria, thus contributing to the high mitochondrial transgene expression.DISCUSSIONTo achieve nuclear transgene expression, a number of useful technologies, including pDNA vectors have been reported to date[2][3][4][5]. Based on such a current trend, many researchers have focused on the mitochondrial targeting of exogenous protein via allotropic expression, where an engineered gene coding a protein fused with a mitochondrial targeting signal peptide (MTS) is transcribed/translated via nuclear transcription/cytosolic translation, and the gene product is then delivered to mitochondria via the MTS import machinery.…”

mentioning

confidence: 99%

Validation of the use of an artificial mitochondrial reporter DNA vector containing a Cytomegalovirus promoter for mitochondrial transgene expression

2017

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Mitochondria have their own gene expression system that is independent of the nuclear system, and control cellular functions in cooperation with the nucleus. While a number of useful technologies for achieving nuclear transgene expression have been reported, only a few have focused on mitochondria. In this study, we validated the utility of an artificial mitochondrial DNA vector with a virus promoter on mitochondrial transgene expression. We designed and constructed pCMV-mtLuc (CGG) that contains a CMV promotor derived from Cytomegalovirus and an artificial mitochondrial genome with a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system. Nluc luciferase activity measurements showed that the pCMV-mtLuc (CGG) efficiently produced the Nluc luciferase protein in human HeLa cells. Moreover, we optimized the mitochondrial transfection of pCMV-mtLuc (CGG) using a MITO-Porter system, a liposome-based carrier for mitochondrial delivery via membrane fusion. As a result, we found that transfection of pCMV-mtLuc (CGG) by MITO-Porter modified with the KALA peptide (cationic amphipathic cell-penetrating peptide) showed a high mitochondrial transgene expression. The developed mitochondrial transgene expression system represents a potentially useful tool for the fields of nanoscience and nanotechnology for controlling the intracellular microenvironment via the regulation of mitochondrial function and promises to open additional innovative research fields of study.

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“Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years”

Cited by 10 publications

References 254 publications

Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells

Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells

Nonviral Gene Delivery with Cationic Glycopolymers

Validation of the use of an artificial mitochondrial reporter DNA vector containing a Cytomegalovirus promoter for mitochondrial transgene expression

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