A safe delivery system to prevent COVID-19 transmission without negative-pressure isolation delivery rooms: experience from a hospital with nosocomial outbreak

AbstractRecent advances in molecular biology have led to the CRISPR revolution, but the lack of an efficient and safe delivery system into cells and tissues continues to hinder clinical translation of CRISPR approaches. Polymeric vectors offer an attractive alternative to viruses as delivery vectors due to their large packaging capacity and safety profile. In this paper, we have demonstrated the potential use of a highly branched poly(β-amino ester) polymer, HPAE-EB, to enable genomic editing via CRISPRCas9-targeted genomic excision of exon 80 in the COL7A1 gene, through a dual-guide RNA sequence system. The biophysical properties of HPAE-EB were screened in a human embryonic 293 cell line (HEK293), to elucidate optimal conditions for efficient and cytocompatible delivery of a DNA construct encoding Cas9 along with two RNA guides, obtaining 15–20% target genomic excision. When translated to human recessive dystrophic epidermolysis bullosa (RDEB) keratinocytes, transfection efficiency and targeted genomic excision dropped. However, upon delivery of CRISPR–Cas9 as a ribonucleoprotein complex, targeted genomic deletion of exon 80 was increased to over 40%. Our study provides renewed perspective for the further development of polymer delivery systems for application in the gene editing field in general, and specifically for the treatment of RDEB.

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Delivery of miRNA Using Fe2O3 Nanoparticles Capped Polyethyleneimine as a Nonviral Carrier

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.531-532.543 ◽

2012 ◽

Vol 531-532 ◽

pp. 543-546

Author(s):

Gao Feng Liang ◽

Ping Li ◽

Wan Jun Lei

Keyword(s):

Delivery System ◽

Hepg2 Cells ◽

Transfection Efficiency ◽

Weight Ratio ◽

Cationic Liposome ◽

Expression Plasmid ◽

Safe Delivery ◽

Rna Interfering ◽

Dna Complex ◽

Gfp Tag

An efﬁcient and safe delivery system of RNA interfering is required for clinical application of gene therapy. The study aimed to develop Fe2O3-based nanoparticles for gene delivery to overcome the disadvantages of polyethyleneimine (PEI) or cationic liposome as gene carrier including the cytotoxicity caused by positive charge and aggregation in the cells surface. PEI-capped Fe2O3 nanoparticles are successfully manufactured utilizing Fe2O3 as core, PEI as carapace, which bind miRNA at an appropriate weight ratio by electrostatic interaction and result in well-dispersed nanoparticles. The synthesized GFP tag with miR-26a expression plasmid was used for monitoring transfection efficiency in HepG2 cells. The nanocomplex exhibited higher transfection efficiency and lower cytotoxicity in HepG2 cells than the PEI/DNA complex and commercially available liposome. The delivery resulted in a significantly upregulation of miR-26a in HepG2 cells. Our results offer an alternate delivery system for RNA interfering that can be used on any gene of interest.

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Mitomycin C-treated human-induced pluripotent stem cells as a safe delivery system of gold nanorods for targeted photothermal therapy of gastric cancer

Nanoscale ◽

10.1039/c6nr06851k ◽

2017 ◽

Vol 9 (1) ◽

pp. 334-340 ◽

Cited By ~ 18

Author(s):

Meng Yang ◽

Yanlei Liu ◽

Wenxiu Hou ◽

Xiao Zhi ◽

Chunlei Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Mitomycin C ◽

Delivery System ◽

Gold Nanorods ◽

Pluripotent Stem Cells ◽

Photothermal Therapy ◽

Safe Delivery ◽

Induced Pluripotent

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N-Type Doping by Plasma Ion Implantation Using a PH3 SDS System

MRS Proceedings ◽

10.1557/proc-438-351 ◽

1996 ◽

Vol 438 ◽

Cited By ~ 3

Author(s):

Shu Qin ◽

Yuanzhong Zhou ◽

Keith Warner ◽

Chung Chan ◽

Jiqun Shao ◽

...

Keyword(s):

Ion Implantation ◽

Sheet Resistance ◽

Delivery System ◽

Lower Pressure ◽

Contamination Level ◽

Si Substrate ◽

Safe Delivery ◽

First Time ◽

Etching Effect

AbstractPH3 SDS (safe delivery system) gas was used for the first time in P11 doping experiments to fabricate n+p junctions and NMOS devices. Two gas recipes (PH3 diluted in H2 and He) were investigated. Under lower pressure, a minimum etching effect was observed. A 4x1015/cm2 phosphorus dose and a 22 Ω/□ sheet resistance were achieved in 4 seconds. Very low contamination level was involved. An anomalous tail of P profile in Si substrate was observed using SIMS measurements.

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Porous Maltodextrin-Based Nanoparticles: A Safe Delivery System for Nasal Vaccines

Journal of Nanomaterials ◽

10.1155/2018/9067195 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Rodolphe Carpentier ◽

Anne Platel ◽

Norhane Salah ◽

Fabrice Nesslany ◽

Didier Betbeder

Keyword(s):

Delivery System ◽

Antigen Delivery ◽

Airway Epithelial ◽

Anionic Phospholipid ◽

Safe Delivery ◽

Human Dose ◽

Epithelial Cell Lines ◽

Cationic Compounds

Vaccination faces limitations, and delivery systems additionally appear to have potential as tools to trigger protective immune responses against diseases. The nanoparticles studied are cationic maltodextrin-based nanoparticles with an anionic phospholipid core (NPL); they are a promising antigen delivery system, and their efficacy as drug vectors against complex diseases such as toxoplasmosis has already been demonstrated. Cationic compounds are generally described as toxic; therefore, it is of interest to evaluate the behavior of these NPL in vitro and in vivo. Here, we studied the in vitro toxicity (cytotoxicity and ROS induction in intestinal and airway epithelial cell lines) and the in vivo tolerability and genotoxicity of these nanoparticles administered by the nasal route to a rodent model. In vitro, these NPL were not cytotoxic and did not induce any ROS production. In vivo, even at very large doses (1000 times the expected human dose), no adverse effect and no genotoxicity were observed in lungs, stomach, colon, or liver. This study shows that these NPL can be safely used.

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Biocompatible nanoparticle PLGA is a noble safe delivery system for embryo development and next generations

Fertility and Sterility ◽

10.1016/j.fertnstert.2017.07.465 ◽

2017 ◽

Vol 108 (3) ◽

pp. e154

Author(s):

H. Song ◽

Y. Kim ◽

J. Park ◽

M. Park ◽

S. Lyu ◽

...

Keyword(s):

Embryo Development ◽

Delivery System ◽

Safe Delivery ◽

Biocompatible Nanoparticle

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Receptor-Mediated Gene Delivery into Antigen Presenting Cells Using Mannosylated Chitosan/DNA Nanoparticles

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.434 ◽

2006 ◽

Vol 6 (9) ◽

pp. 2796-2803 ◽

Cited By ~ 84

Author(s):

Tae Hee Kim ◽

Jae Woon Nah ◽

Myung-Haing Cho ◽

Tae Gwan Park ◽

Chong Su Cho

Keyword(s):

Gene Transfer ◽

Gene Delivery ◽

Delivery System ◽

Viral Vectors ◽

Antigen Presenting Cells ◽

Water Soluble ◽

Gene Delivery System ◽

Great Ability ◽

Safe Delivery ◽

Antigen Presenting

Dendritic cells (DCs) are professional antigen presenting cells that induce, sustain, and regulate immune responses. Gene modification of DCs is of particular interest for immunotherapy of diseases where the immunes system has failed or is abnormally regulated, such as in cancer or autoimmune disease. Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic DNA. Among various non-viral vectors, chitosan is considered to be a good candidate for gene delivery system, however, lack of cell specificity and low transfection of chitosan need to be overcome prior to clinical use. In this study, mannosylated chitosan (MC) was prepared to induce the receptor-mediated endocytosis and targeting into antigen presenting cells (APCs), especially DCs having mannose receptors. MC showed great ability to form complexes with DNA and showed suitable physicochemical properties for gene delivery system. It had low cytotoxicity and exhibited much enhanced gene transfer efficiency on the macrophage cell line than chitosan itself. Also, MC/DNA complex was more efficient for transferring IL-12 gene into DCs rather than water-soluble chitosan (WSC)/DNA one, which resulted in better induction of INF-γ from DCs. Therefore, MC is a promising gene delivery system for repeated administration to maintain sustained gene expression, thereby opening the possibility for immunotherapy.

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