Design and synthesis of a polyguanidium vector with enhanced DNA binding ability for effective gene delivery at a low N/P ratio

2020 ◽  
Vol 11 (3) ◽  
pp. 664-668 ◽  
Author(s):  
Zhiyong Chen ◽  
Wei Huang ◽  
Nan Zheng ◽  
Yugang Bai

A polyguanidium polymer has extra affinity toward DNA and can mediate transfection efficiently at a low polymer to DNA ratio.

2007 ◽  
Vol 342-343 ◽  
pp. 457-460 ◽  
Author(s):  
You Kyoung Kim ◽  
In Kyu Park ◽  
Hu Lin Jiang ◽  
Rohidas B. Arote ◽  
Hwan Jeong Jeong ◽  
...  

Polypropylenimine (PPI) dendrimers have been used by many researchers as gene delivery carriers due to their high functionality. Glucose as a kind of carbohydrate is biocompatible and hydrophilic. In this study, we synthesized glucosylated PPI (G-PPI) dendrimers to reduce cytotoxicity. Glucose substitution of G-PPI dendrimers was determined by the sulfuric acid micromethod. The G-PPI dendrimer was complexed with plasmid DNA in various N/P ratios, and the complex was characterized. G-PPI dendrimers showed good DNA binding ability and high protection of DNA from nuclease attack. The G-PPI dendrimer had low cytotoxicity compared to PPI dendrimer by cytotoxicity assay. Also, transfection efficiency was influenced by glucosylation degree and the transfection efficiency for the G-PPI-5 was slightly higher than that of PPI dendrimer in HeLa cell line.


2015 ◽  
Vol 815 ◽  
pp. 401-406 ◽  
Author(s):  
Qing Wen Guan ◽  
Min Wang

Gene therapy has great potential in offering highly promising treatments for cancer. Polymer-metal hybrid nanoparticles (NPs) are good candidates as gene delivery vehicles due to their unique properties and facile functionalization. The polymer component in hybrid NPs can provide accurate cancer cell targeting and high DNA binding ability while the metallic component can provide imaging functions for the nanodevices. In the present study, hybrid NPs comprising an Au-Ag bimetallic core and a folic acid-chitosan shell (Au-Ag@CS-FA) were fabricated. The structure and relevant properties of Au-Ag@CS-FA NPs were subsequently studied using a variety of techniques,like scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), transmission electron microscope (TEM) and UV-visible spectra. Their DNA binding ability was also assessed. Results showed that Au-Ag@CS-FA NPs possessed properties that can make them excellent gene delivery vehicles.


1994 ◽  
Vol 14 (11) ◽  
pp. 7557-7568 ◽  
Author(s):  
J Zuo ◽  
R Baler ◽  
G Dahl ◽  
R Voellmy

Heat stress regulation of human heat shock genes is mediated by human heat shock transcription factor hHSF1, which contains three 4-3 hydrophobic repeats (LZ1 to LZ3). In unstressed human cells (37 degrees C), hHSF1 appears to be in an inactive, monomeric state that may be maintained through intramolecular interactions stabilized by transient interaction with hsp70. Heat stress (39 to 42 degrees C) disrupts these interactions, and hHSF1 homotrimerizes and acquires heat shock element DNA-binding ability. hHSF1 expressed in Xenopus oocytes also assumes a monomeric, non-DNA-binding state and is converted to a trimeric, DNA-binding form upon exposure of the oocytes to heat shock (35 to 37 degrees C in this organism). Because endogenous HSF DNA-binding activity is low and anti-hHSF1 antibody does not recognize Xenopus HSF, we employed this system for mapping regions in hHSF1 that are required for the maintenance of the monomeric state. The results of mutagenesis analyses strongly suggest that the inactive hHSF1 monomer is stabilized by hydrophobic interactions involving all three leucine zippers which may form a triple-stranded coiled coil. Trimerization may enable the DNA-binding function of hHSF1 by facilitating cooperative binding of monomeric DNA-binding domains to the heat shock element motif. This view is supported by observations that several different LexA DNA-binding domain-hHSF1 chimeras bind to a LexA-binding site in a heat-regulated fashion, that single amino acid replacements disrupting the integrity of hydrophobic repeats render these chimeras constitutively trimeric and DNA binding, and that LexA itself binds stably to DNA only as a dimer but not as a monomer in our assays.


1991 ◽  
Vol 5 (10) ◽  
pp. 1902-1911 ◽  
Author(s):  
K D Sarge ◽  
V Zimarino ◽  
K Holm ◽  
C Wu ◽  
R I Morimoto

2021 ◽  
Author(s):  
Chaofan Peng ◽  
Yuqian Tan ◽  
Peng Yang ◽  
Kangpeng Jin ◽  
Chuan Zhang ◽  
...  

Abstract BackgroundEmerging studies have investigated circRNAs as significant regulation factors in multiple cancer progression. Nevertheless, the biological functions and underlying mechanisms of circRNAs in colorectal cancer progression remain unclear.MethodsA novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of phenotype experiments in vitro and vivo were performed to investigate the role of circ-GALNT16 in CRC. FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were constructed to explore the molecular mechanisms of circ-GALNT16 in colorectal cancer.ResultsCirc-GALNT16 was downregulated in colorectal cancer and negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastasis ability of colorectal cancer in vitro and vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which resulted in the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. Furthermore, RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex.ConclusionsCirc-GALNT16 suppressed CRC progression via inhibiting Serpine1 expression through adjusting the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might work as a biomarker and therapeutic target for CRC.


2018 ◽  
Vol 47 (38) ◽  
pp. 13573-13591 ◽  
Author(s):  
Kimberley J. Davis ◽  
Nawal M. O. Assadawi ◽  
Son Q. T. Pham ◽  
Monica L. Birrento ◽  
Christopher Richardson ◽  
...  

The synthesis of two new series of nickel complexes is described, along with their ability to bind to duplex and quadruplex DNA structures.


Sign in / Sign up

Export Citation Format

Share Document