scholarly journals Coupling of RAFT polymerization and chemoselective post-modifications of elastin-like polypeptides for the synthesis of gene delivery hybrid vectors

2021 ◽  
Author(s):  
Lourdes Mónica Bravo-Anaya ◽  
Julien Rosselgong ◽  
Karla Gricelda Fernández-Solís ◽  
Ye Xiao ◽  
Amélie Vax ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Nucleic Acids ◽  
Raft Polymerization ◽  
Hybrid Vectors ◽  
Specific Number

Hybrid cationic ELPs for nucleic acids transport and delivery were synthetized through the coupling of RAFT polymerization and biorthogonal chemistry of ELPs, introducing a specific number of positive charges to the ELP backbone.

Exosome as a Natural Gene Delivery Vector for Cancer Treatment

2020 ◽  
Vol 20 (11) ◽  
pp. 821-830
Author(s):  
Prasad Pofali ◽  
Adrita Mondal ◽  
Vaishali Londhe
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Cancer Treatment ◽  
Intestinal Barrier ◽  
Gene Carrier ◽  
Gene Delivery Vector ◽  
Delivery Vector

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier. Objective: This review focusses on the role of exosome as a carrier to efficiently deliver a gene for cancer treatment and diagnosis. The methods for loading of nucleic acids onto the exosomes, advantages of exosomes as a smart intercellular shuttle for gene delivery and therapeutic applications as a gene delivery vector for siRNA, miRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and also the limitations of exosomes as a gene carrier are all reviewed in this article. Methods: Mostly, electroporation and chemical transfection are used to prepare gene loaded exosomes. Results: Exosome-mediated delivery is highly promising and advantageous in comparison to the current delivery methods for systemic gene therapy. Targeted exosomes, loaded with therapeutic nucleic acids, can efficiently promote the reduction of tumor proliferation without any adverse effects. Conclusion: In the near future, exosomes can become an efficient gene carrier for delivery and a biomarker for the diagnosis and treatment of cancer.

scholarly journals In vivo magnetofection: a novel approach for targeted topical delivery of nucleic acids for rectoanal motility disorders

2018 ◽  
Vol 314 (1) ◽  
pp. G109-G118 ◽  
Author(s):  
Jagmohan Singh ◽  
Ipsita Mohanty ◽  
Satish Rattan
Keyword(s):  
Smooth Muscle ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Internal Anal Sphincter ◽  
Fecal Pellet ◽  
Muscle Layer ◽  
Motility Disorders ◽  
Circular Smooth Muscle ◽  
Novel Approach

In these studies, we developed a novel approach of in vivo magnetofection for localized delivery of nucleic acids such as micro-RNA-139-5p (miR-139-5p; which is known to target Rho kinase2) to the circular smooth muscle layer of the internal anal sphincter (IAS). The IAS tone is known to play a major role in the rectoanal continence via activation of RhoA-associated kinase (RhoA/ROCK2). These studies established an optimized protocol for efficient gene delivery using an assembly of equal volumes of in vivo PolyMag and miR139-5p or anti-miR-139-5p (100 nM each) injected in the circular smooth muscle layer in the pinpointed areas of the rat perianal region and then incubated for 20 min under magnetic field. Magnetofection efficiency was confirmed and analyzed by confocal microscopy of FITC-tagged siRNA. Using physiological and biochemical approaches, we investigated the effects of miR-139-5p and anti-miR-139-5p on basal intraluminal IAS pressure (IASP), fecal pellet count, IAS tone, agonist-induced contraction, contraction-relaxation kinetics, and RhoA/ROCK2 signaling. Present studies demonstrate that magnetofection-mediated miR-139-5p delivery significantly decreased RhoA/ROCK2, p-MYPT1, and p-MLC20 signaling, leading to decreases in the basal IASP and IAS tone and in rates of contraction and relaxation associated with increase in fecal pellet output. Interestingly, anti-miR-139-5p transfection had opposite effects on these parameters. Collectively, these data demonstrate that magnetofection is a promising novel method of in vivo gene delivery and of nucleotides to the internal anal sphincter for the site-directed and targeted therapy for rectoanal motility disorders. NEW & NOTEWORTHY These studies for the first time demonstrate the success of topical in vivo magnetofection (MF) of nucleic acids using perianal injections. To demonstrate its effectiveness, we used FITC-tagged siRNA via immunofluorescence microcopy and functional and biochemical evidence using miR-139-5p (which is known to target ROCK2). In conclusion, MF allows safe, convenient, efficient, and targeted delivery of oligonucleotides such as siRNAs and microRNAs. These studies have direct therapeutic implications in rectoanal motility disorders especially associated with IAS.

scholarly journals Transplacental Gene Delivery (TPGD) as a Noninvasive Tool for Fetal Gene Manipulation in Mice

2019 ◽  
Vol 20 (23) ◽  
pp. 5926 ◽  
Author(s):  
Nakamura ◽  
Watanabe ◽  
Ando ◽  
Ishihara ◽  
Sato
Keyword(s):  
Gene Delivery ◽  
Nucleic Acids ◽  
Myocardial Cells ◽  
Transcription Activator ◽  
Exogenous Dna ◽  
Cell Functions ◽  
Fetal Tissues ◽  
Potential Applications ◽  
Pregnant Mice ◽  
Basic Studies

Transplacental gene delivery (TPGD) is a technique for delivering nucleic acids to fetal tissues via tail-vein injections in pregnant mice. After transplacental transport, administered nucleic acids enter fetal circulation and are distributed among fetal tissues. TPGD was established in 1995 by Tsukamoto et al., and its mechanisms, and potential applications have been further characterized since. Recently, discoveries of sequence specific nucleases, such as zinc-finger nuclease (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) (CRISPR/Cas9), have revolutionized genome editing. In 2019, we demonstrated that intravenous injection of plasmid DNA containing CRISPR/Cas9 produced indels in fetal myocardial cells, which are comparatively amenable to transfection with exogenous DNA. In the future, this unique technique will allow manipulation of fetal cell functions in basic studies of fetal gene therapy. In this review, we describe developments of TPGD and discuss their applications to the manipulation of fetal cells.

scholarly journals Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles

2014 ◽  
Vol 2 (46) ◽  
pp. 8142-8153 ◽  
Author(s):  
Cheng-Hsiang Kuo ◽  
Lorraine Leon ◽  
Eun Ji Chung ◽  
Ru-Ting Huang ◽  
Timothy J. Sontag ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Nucleic Acids ◽  
Enzymatic Degradation ◽  
Polyelectrolyte Complex ◽  
Specific Interactions ◽  
Delivery Vehicles ◽  
Complex Micelles ◽  
Gene Delivery Vehicles

Polyelectrolyte complex micelles have great potential as gene delivery vehicles because of their ability to encapsulate charged nucleic acids forming a core by neutralizing their charge, while simultaneously protecting the nucleic acids from non-specific interactions and enzymatic degradation.

scholarly journals Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

Polymers ◽  
2011 ◽  
Vol 3 (2) ◽  
pp. 693-718 ◽  
Author(s):  
Olga Samsonova ◽  
Christian Pfeiffer ◽  
Markus Hellmund ◽  
Olivia M. Merkel ◽  
Thomas Kissel
Keyword(s):  
Molecular Weight ◽  
Block Copolymers ◽  
Gene Delivery ◽  
Raft Polymerization ◽  
Viral Gene ◽  
Low Molecular Weight ◽  
Viral Gene Delivery

High-Effective Gene Delivery Based on Cyclodextrins Multivalent Assembly in Target Cancer Cells

2022 ◽  
Author(s):  
Yao-Hua Liu ◽  
Yu Liu
Keyword(s):  
Gene Therapy ◽  
Controlled Release ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Cancer Cells ◽  
Chemical Biology ◽  
Supramolecular Assembly ◽  
Target Cancer

Nucleic acids condensation and controlled release remain significant challenges of gene therapy in chemical biology and nanotechnology fields. In this work, we have reported a polysaccharide supramolecular assembly constructed by...

Transdermal Delivery of Poly-Hyaluronic Acid-Based Spherical Nucleic Acids for Chemogene Therapy

Nanoscale ◽  
2022 ◽  
Author(s):  
Kai Jiang ◽  
Di Zhao ◽  
Rui Ye ◽  
Xinlong Liu ◽  
Chao Gao ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Nucleic Acid ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Delivery System ◽  
Transdermal Delivery ◽  
Gene Delivery System ◽  
Transdermal Administration ◽  
Spherical Nucleic Acid ◽  
Spherical Nucleic Acids

Spherical nucleic acid (SNA), as a good gene delivery system, has a good application prospect for transdermal administration in skin disorders treatment. However, most of traditional SNA core materials are...

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