scholarly journals Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery

2012 ◽  
Vol 7 (6) ◽  
pp. 389-393 ◽  
Author(s):  
Hyukjin Lee ◽  
Abigail K. R. Lytton-Jean ◽  
Yi Chen ◽  
Kevin T. Love ◽  
Angela I. Park ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Sirna Delivery ◽  
Self Assembled

scholarly journals Novel fusion peptide‐mediated siRNA delivery using self‐assembled nanocomplex

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyung Ah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
Byeong Hee Hwang
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Viral Infections ◽  
Immune Cell ◽  
Sirna Delivery ◽  
Cellular Membrane ◽  
Fusion Peptides ◽  
Self Assembled

Abstract Background Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Results Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. Conclusions The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

scholarly journals Evolution from Covalent to Self-Assembled PAMAM-Based Dendrimers as Nanovectors for siRNA Delivery in Cancer by Coupled in Silico-Experimental Studies. Part II: Self-Assembled siRNA Nanocarriers

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 324 ◽  
Author(s):  
Erik Laurini ◽  
Domenico Marson ◽  
Suzana Aulic ◽  
Maurizio Fermeglia ◽  
Sabrina Pricl
Keyword(s):  
Cancer Cells ◽  
Large Scale ◽  
Sirna Delivery ◽  
Experimental Studies ◽  
Good Manufacturing Practice ◽  
Surface Groups ◽  
Molecular Architecture ◽  
Self Assembled

In part I of this review, the authors showed how poly(amidoamine) (PAMAM)-based dendrimers can be considered as promising delivering platforms for siRNA therapeutics. This is by virtue of their precise and unique multivalent molecular architecture, characterized by uniform branching units and a plethora of surface groups amenable to effective siRNA binding and delivery to e.g., cancer cells. However, the successful clinical translation of dendrimer-based nanovectors requires considerable amounts of good manufacturing practice (GMP) compounds in order to conform to the guidelines recommended by the relevant authorizing agencies. Large-scale GMP-standard high-generation dendrimer production is technically very challenging. Therefore, in this second part of the review, the authors present the development of PAMAM-based amphiphilic dendrons, that are able to auto-organize themselves into nanosized micelles which ultimately outperform their covalent dendrimer counterparts in in vitro and in vivo gene silencing.

scholarly journals Novel Fusion Peptide-Mediated siRNA Delivery Using Self-Assembled Nanocomplex

2020 ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyungah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
Byeong Hee Hwang
Keyword(s):  
Gene Therapy ◽  
Gene Silencing ◽  
Cellular Uptake ◽  
Viral Infections ◽  
Sirna Delivery ◽  
Cellular Membrane ◽  
Fusion Peptides ◽  
Self Assembled

Abstract Background: Gene therapy using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine.Results: Among the novel fusion peptides and siRNAs, nanocomplexes have outstanding cellular uptake and gene silencing effect in vitro and high stability and retention effect of siRNAs in vivo. Oligo arginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased stability and retention of siRNAs at the site of the tumor. Conclusions: The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene therapy.

Solvent-driven, self-assembled acid-responsive poly(ketalized serine)/siRNA complexes for RNA interference

2020 ◽  
Vol 8 (23) ◽  
pp. 6718-6729
Author(s):  
Shirley Wong ◽  
Jessica A. Kemp ◽  
Min Suk Shim ◽  
Young Jik Kwon
Keyword(s):  
Rna Interference ◽  
Nucleic Acid ◽  
Sirna Delivery ◽  
Endosomal Escape ◽  
Self Assembled

Self-assembled, biocompatible poly(kSer)/siRNA complexes demonstrate efficient nucleic acid encapsulation, internalization, endosomal escape, and acid-triggered cargo release, tackling multiple hurdles in siRNA delivery.

A flexible microneedle array as low-voltage electroporation electrodes for in vivo DNA and siRNA delivery

Lab on a Chip ◽  
2014 ◽  
Vol 14 (20) ◽  
pp. 4093-4102 ◽  
Author(s):  
Zewen Wei ◽  
Shuquan Zheng ◽  
Renxin Wang ◽  
Xiangli Bu ◽  
Huailei Ma ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Low Voltage ◽  
Sirna Delivery ◽  
Nucleic Acid Delivery ◽  
Microneedle Array ◽  
Array Electrode

A flexible microneedle array electrode chip for low-voltage electroporation with good tissue adaptation, efficient nucleic acid delivery, and minimum damage.

scholarly journals Sugar Functionalized Synergistic Dendrimers for Biocompatible Delivery of Nucleic Acid Therapeutics

Polymers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1034 ◽  
Author(s):  
Shuqin Han ◽  
Tsogzolmaa Ganbold ◽  
Qingming Bao ◽  
Takashi Yoshida ◽  
Huricha Baigude
Keyword(s):  
Nucleic Acid ◽  
Sirna Delivery ◽  
Green Fluorescence Protein ◽  
Nucleic Acid Delivery ◽  
Cationic Polymers ◽  
Nucleic Acid Therapeutics ◽  
Fluorescence Protein ◽  
Interfering Rna

Sugars containing cationic polymers are potential carriers for in vitro and in vivo nucleic acid delivery. Monosaccharides such as glucose and galactose have been chemically conjugated to various materials of synergistic poly-lysine dendrimer systems for efficient and biocompatible delivery of short interfering RNA (siRNA). The synergistic dendrimers, which contain lipid conjugated glucose terminalized lysine dendrimers, have significantly lower adverse impact on cells while maintaining efficient cellular entry. Moreover, the synergistic dendrimers complexed to siRNA induced RNA interference (RNAi) in the cells and profoundly knocked down green fluorescence protein (GFP) as well as the endogenously expressing disease related gene Plk1. The new synergic dendrimers may be promising system for biocompatible and efficient siRNA delivery.

scholarly journals Novel fusion peptide-mediated siRNA delivery using self-assembled nanocomplex

2021 ◽  
Author(s):  
Yeong Chae Ryu ◽  
Kyungah Kim ◽  
Byoung Choul Kim ◽  
Hui-Min David Wang ◽  
BYEONG HEE HWANG
Keyword(s):  
Gene Silencing ◽  
Cellular Uptake ◽  
Viral Infections ◽  
Sirna Delivery ◽  
Cellular Membrane ◽  
Fusion Peptides ◽  
Genetic Level ◽  
Self Assembled

Abstract Background: Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine.Results: Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without immunogenicity.Conclusions: The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery

2013 ◽  
Vol 9 (8) ◽  
pp. 7746-7757 ◽  
Author(s):  
Daoshu Lin ◽  
Qian Jiang ◽  
Qiang Cheng ◽  
Yuanyu Huang ◽  
Pingsheng Huang ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Self Assembled

scholarly journals Evolution from Covalent to Self-Assembled PAMAM-Based Dendrimers as Nanovectors for siRNA Delivery in Cancer by Coupled In Silico-Experimental Studies. Part I: Covalent siRNA Nanocarriers

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 351 ◽  
Author(s):  
Domenico Marson ◽  
Erik Laurini ◽  
Suzana Aulic ◽  
Maurizio Fermeglia ◽  
Sabrina Pricl
Keyword(s):  
Sirna Delivery ◽  
Experimental Studies ◽  
Short Review ◽  
Companion Paper ◽  
Small Interfering Rnas ◽  
New Approach ◽  
Amphiphilic Dendrimers ◽  
Self Assembled

Small interfering RNAs (siRNAs) represent a new approach towards the inhibition of gene expression; as such, they have rapidly emerged as promising therapeutics for a plethora of important human pathologies including cancer, cardiovascular diseases, and other disorders of a genetic etiology. However, the clinical translation of RNA interference (RNAi) requires safe and efficient vectors for siRNA delivery into cells. Dendrimers are attractive nanovectors to serve this purpose, as they present a unique, well-defined architecture and exhibit cooperative and multivalent effects at the nanoscale. This short review presents a brief introduction to RNAi-based therapeutics, the advantages offered by dendrimers as siRNA nanocarriers, and the remarkable results we achieved with bio-inspired, structurally flexible covalent dendrimers. In the companion paper, we next report our recent efforts in designing, characterizing and testing a series of self-assembled amphiphilic dendrimers and their related structural alterations to achieve unprecedented efficient siRNA delivery both in vitro and in vivo.

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