Cyclic Poly(ß-amino ester)s with Enhanced Gene Transfection Activity Synthesized through Intra-molecular Cyclization

2022 ◽  
Author(s):  
Chenfei Wang ◽  
Xiaobei Huang ◽  
Litao Sun ◽  
Qiuxia Li ◽  
Zhili Li ◽  
...  
Keyword(s):  
Free Radical ◽  
Gene Delivery ◽  
Michael Addition ◽  
Topological Structure ◽  
Gene Transfection ◽  
Critical Role ◽  
Ring Closure ◽  
Amino Ester ◽  
Cationic Polymers

Topological structure plays a critical role in gene delivery of cationic polymers. Cyclic poly(ß-amino ester)s (CPAEs) are successfully synthesized via sequential Michael addition and free radical initiating ring-closure reaction. CPAE...

Micelle-like luminescent nanoparticles as a visible gene delivery system with reduced toxicity

2015 ◽  
Vol 3 (42) ◽  
pp. 8394-8400 ◽  
Author(s):  
Keni Yang ◽  
Shengliang Li ◽  
Shubin Jin ◽  
Xiangdong Xue ◽  
Tingbin Zhang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Gene Transfection ◽  
Gene Delivery System ◽  
Cationic Polymers ◽  
Luminescent Nanoparticles ◽  
Reduced Toxicity

Luminescent nanoparticles (TPEI) were synthesized to tackle the undesired cytotoxicity of cationic polymers and were also used for visible gene transfection.

scholarly journals The transition from linear to highly branched poly(β-amino ester)s: Branching matters for gene delivery

2016 ◽  
Vol 2 (6) ◽  
pp. e1600102 ◽  
Author(s):  
Dezhong Zhou ◽  
Lara Cutlar ◽  
Yongsheng Gao ◽  
Wei Wang ◽  
Jonathan O’Keeffe-Ahern ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Branched Polymers ◽  
Nonviral Gene Delivery ◽  
Great Promise ◽  
Amino Ester ◽  
Design And Synthesis ◽  
Gene Delivery Vectors

Nonviral gene therapy holds great promise but has not delivered treatments for clinical application to date. Lack of safe and efficient gene delivery vectors is the major hurdle. Among nonviral gene delivery vectors, poly(β-amino ester)s are one of the most versatile candidates because of their wide monomer availability, high polymer flexibility, and superior gene transfection performance both in vitro and in vivo. However, to date, all research has been focused on vectors with a linear structure. A well-accepted view is that dendritic or branched polymers have greater potential as gene delivery vectors because of their three-dimensional structure and multiple terminal groups. Nevertheless, to date, the synthesis of dendritic or branched polymers has been proven to be a well-known challenge. We report the design and synthesis of highly branched poly(β-amino ester)s (HPAEs) via a one-pot “A2 + B3 + C2”–type Michael addition approach and evaluate their potential as gene delivery vectors. We find that the branched structure can significantly enhance the transfection efficiency of poly(β-amino ester)s: Up to an 8521-fold enhancement in transfection efficiency was observed across 12 cell types ranging from cell lines, primary cells, to stem cells, over their corresponding linear poly(β-amino ester)s (LPAEs) and the commercial transfection reagents polyethyleneimine, SuperFect, and Lipofectamine 2000. Moreover, we further demonstrate that HPAEs can correct genetic defects in vivo using a recessive dystrophic epidermolysis bullosa graft mouse model. Our findings prove that the A2 + B3 + C2 approach is highly generalizable and flexible for the design and synthesis of HPAEs, which cannot be achieved by the conventional polymerization approach; HPAEs are more efficient vectors in gene transfection than the corresponding LPAEs. This provides valuable insight into the development and applications of nonviral gene delivery and demonstrates great prospect for their translation to a clinical environment.

Rapid Optimization of Gene Delivery by Parallel End-modification of Poly(β-amino ester)s

2007 ◽  
Author(s):  
Gregory T Zugates ◽  
Weidan Peng ◽  
Andreas Zumbuehl ◽  
Siddharth Jhunjhunwala ◽  
Yu-Hung Huang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Amino Ester

Polyplex: A Promising Gene Delivery System

2019 ◽  
Vol 12 (6) ◽  
pp. 4681-4686
Author(s):  
Rohan Aggarwal ◽  
Monika Targhotra ◽  
Bhumika Kumar ◽  
P.K Sahoo ◽  
Meenakshi K Chauhan
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Delivery System ◽  
Viral Vectors ◽  
Gene Delivery System ◽  
Cationic Polymers ◽  
Therapeutic Application ◽  
Promising Alternative ◽  
Structure And Stability ◽  
The Past

In the past few years gene delivery system has gained a huge attention owing to its proved efficacy in several diseases especially in those caused by genetic and/oroncological malfunctioning. The effective gene delivery mainly depends on the carrier molecules that can ensure the safe and specific delivery of the nucleic acidmolecules. Viral vectors have been used for a longer period as the gene transfer vehicle. However, these viral vectors have potential immunological disadvantages that made them less preferred. Recently, non-viral vectors such as polyplexes have emerged as a promising alternative for viral vectors. Polyplexes are formed by conjugating a polymer with DNA and in maximum cases the cationic polymers are preferred over others. The structure and stability of the polyplexes depends on various factors. The ability of the polymer to condense the DNA mainly dictates the efficiency of the polyplex mediated transfection. In this review we are going to provide a framework for the synthesis and design of the polyplexes along with the structure and stability of the complexes pertaining to mechanism of action, characterization and therapeutic application, including polyethyleneimine mediated cytotoxicity as well as newer strategies for the generation of better polyplexes.

scholarly journals Biopolymeric Materials Used as Nonviral Vectors: A Review

2021 ◽  
Vol 2 (1) ◽  
pp. 100-109
Author(s):  
Jailson de Araújo Santos ◽  
Daniel Barbosa Liarte ◽  
Alessandra Braga Ribeiro ◽  
Marcia dos Santos Rizzo ◽  
Marcília Pinheiro da Costa ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Web Of Science ◽  
Gene Transfection ◽  
Genetic Material ◽  
Nonviral Vectors ◽  
Cationic Polymers ◽  
Genetic Trait ◽  
Low Diversity ◽  
Different Types ◽  
Materials Used

Bacterial transformation and gene transfection can be understood as being the results of introducing specific genetic material into cells, resulting in gene expression, and adding a new genetic trait to the host cell. Many studies have been carried out to investigate different types of lipids and cationic polymers as promising nonviral vectors for DNA transfer. The present study aimed to carry out a systematic review on the use of biopolymeric materials as nonviral vectors. The methodology was carried out based on searches of scientific articles and applications for patents published or deposited from 2006 to 2020 in different databases for patents (EPO, USPTO, and INPI) and articles (Scopus, Web of Science, and Scielo). The results showed that there are some deposits of patents regarding the use of chitosan as a gene carrier. The 16 analyzed articles allowed us to infer that the use of biopolymers as nonviral vectors is limited due to the low diversity of biopolymers used for these purposes. It was also observed that the use of different materials as nonviral vectors is based on chemical structure modifications of the material, mainly by the addition of cationic groups. Thus, the use of biopolymers as nonviral vectors is still limited to only a few polysaccharide types, emphasizing the need for further studies involving the use of different biopolymers in processes of gene transfer.

Catalyst-Free One-Pot Synthesis of Novel Heteroarylamine Substituted Furo[3,2-c]coumarins

Synlett ◽  
2018 ◽  
Vol 29 (12) ◽  
pp. 1589-1592 ◽  
Author(s):  
Abolfazl Olyaei ◽  
Mahnaz Saraei ◽  
Reyhaneh Khoeiniha
Keyword(s):  
Michael Addition ◽  
Aldol Condensation ◽  
Ring Closure ◽  
Dehydration Reaction ◽  
One Pot ◽  
Catalyst Free ◽  
One Pot Synthesis ◽  
Tandem Process ◽  
First Time

A high-yielding cyclocondensation of 4-hydroxycoumarin, phenylglyoxal monohydrate, and heteroarylamines proceeds without catalysis, which gives novel functionalized furo[3,2-c]coumarins and heteroarylamino alkylation of coumarin products in acetonitrile under reflux, is reported for the first time. This tandem process involves sequentially an aldol condensation, Michael addition, a ring closure, and dehydration reaction.

Lipothiophosphoramidates for gene delivery: critical role of the cationic polar headgroup

2012 ◽  
Vol 10 (10) ◽  
pp. 2051 ◽  
Author(s):  
Aurore Fraix ◽  
Tristan Montier ◽  
Tony Le Gall ◽  
Charlotte M. Sevrain ◽  
Nathalie Carmoy ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Critical Role

Brushlike Cationic Polymers with Low Charge Density for Gene Delivery

2017 ◽  
Vol 19 (5) ◽  
pp. 1410-1415 ◽  
Author(s):  
Jonathan O’Keeffe Ahern ◽  
Sigen A ◽  
Dezhong Zhou ◽  
Yongsheng Gao ◽  
Jing Lyu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Charge Density ◽  
Cationic Polymers ◽  
Low Charge

Synthesis of Poly(β-amino ester)s Optimized for Highly Effective Gene Delivery

2003 ◽  
Vol 14 (5) ◽  
pp. 979-988 ◽  
Author(s):  
Akin Akinc ◽  
Daniel G. Anderson ◽  
David M. Lynn ◽  
Robert Langer
Keyword(s):  
Gene Delivery ◽  
Amino Ester ◽  
Highly Effective
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