Cardiovascular gene delivery: The good road is awaiting☆

Brewster, Luke P.; Brey, Eric M.; Greisler, Howard P.

doi:10.1016/j.addr.2006.03.002

Cited by 54 publications

(37 citation statements)

References 230 publications

(189 reference statements)

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“…Although the delivery of nucleic acids in the field of TE is quite auspicious, this approach still remains in its experimental phases, [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] and only a very limited number of studies applies carriers that rely on the described redox potential gradient. [55,56] This review will focus on the redox-potential trigger between the extra-and intracellular environments.…”

Section: Reviewmentioning

confidence: 99%

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

et al. 2009

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Nucleic acids are not only expected to assume a pivotal position as "drugs" in the treatment of genetic and acquired diseases, but could also act as molecular cues to control the microenvironment during tissue regeneration. Despite this promise, the efficient delivery of nucleic acids to their side of action is still the major hurdle. One among many prerequisites for a successful carrier system for nucleic acids is high stability in the extracellular environment, accompanied by an efficient release of the cargo in the intracellular compartment. A promising strategy to create such an interactive delivery system is to exploit the redox gradient between the extra- and intracellular compartments. In this review, emphasis is placed on the biological rationale for the synthesis of redox sensitive, disulfide-based carrier systems, as well as the extra- and intracellular processing of macromolecules containing disulfide bonds. Moreover, the basic synthetic approaches for introducing disulfide bonds into carrier molecules, together with examples that demonstrate the benefit of disulfides at the individual stages of nucleic acid delivery, will be presented.

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Section: Reviewmentioning

confidence: 99%

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

et al. 2009

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“…In addition to the COS-7 and HepG2 immortalized cell lines, end-modified C32 poly(b-amino ester) s were also tested on Human Umbilical Vein Endothelial Cells (HUVECs) since primary endothelial cells are particularly difficult to transfect [12] and an important cell target for treatments against cardiovascular disease [13,14] and cancer. [15] A commercially available GFP-expressing replication-deficient adenoviral vector that uses the same cytomegalovirus (CMV) promoter/enhancer as the plasmid DNA was chosen as a viral vector positive control (Ad5.CMV-GFP).…”

Section: D60-acmentioning

confidence: 99%

Combinatorial Modification of Degradable Polymers Enables Transfection of Human Cells Comparable to Adenovirus

et al. 2007

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Viral gene therapy has high efficacy, but is plagued by serious safety risks, production and manufacturing challenges, and other limitations including nucleic acid cargo capacity. [1] In contrast, non-viral gene delivery systems, while addressing these challenges, remain less effective.[2] Here we develop end-modified poly(b-amino ester)s, easy-to-synthesize degradable polymers, that are able to deliver DNA to primary human umbilical vein endothelial cells (HUVECs) at levels comparable to adenovirus at a Multiplicity of Infection (MOI) between 100 and 500, and two orders of magnitude better than the commonly used non-viral polymeric vector, polyethylenimine (PEI). Interestingly, small structural changes were found to have dramatic effects on multiple steps of gene delivery including the DNA binding affinity, nanoparticle size, intracellular DNA uptake, and final protein expression. In vivo, these polymer modifications dramatically enhance DNA delivery to ovarian tumors. We believe the development of polymeric vectors with gene delivery efficacy comparable to adenovirus could set a new benchmark in nonviral transfection capability. Numerous polymeric materials have been used for gene delivery including poly(L-lysine), polyethylenimine, poly(amidoamine) dendrimers, poly(a-[4-aminobutyl]-L-glycolic acid), chitosan, cyclodextrin, and others. [2,3] While significant strides have been made in improving delivery, efficacy remains generally low, particularly for primary cells in the presence of serum.[4] Poly(b-amino ester) s are promising materials that bind and self-assemble with DNA to form stable nanoparticles that effectively enter cells, escape the endosomal compartments, and degrade via hydrolytic cleavage of backbone ester groups. [5][6][7][8] While good in vitro and in vivo activity has been described, [5,9] structural diversity of existing poly(b-amino ester) was limited by chemical requirements of conjugate addition. [5][6][7][8]10] We hypothesized that the exploration of an expanded chemical space through combinatorial modification of poly(b-amino ester) s could optimize performance. To this end, and to better understand structure-function relationships, we synthesized a library of end-modified poly(b-amino ester) s using three base diacrylate-terminated polymers and twelve amine end-capping reagents (Fig. 1). Chemical methods were developed to allow a simple, one step modification of base polymers with several different amine capping agents (see methods). In this way, the combined effects of internal structure and amine termination on poly(b-amino ester) transfections could be systematically assessed. Once synthesized, polymers were characterized by 1 H NMR and GPC (see methods).Three different polymers were chosen for end modification: C32, D60 and C20 (Fig. 1B). High-throughput screening studies have identified polymer C32 as the most effective poly(bamino ester) to date for gene delivery. [5,6] Another polymer, D60 is also an effective gene delivery agent, but with a structure significantly different from...

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“…Thus, the selective promotion and competition of ECs with other cells such as SMCs are crucial to successfully realize in situ endothelialization. [13,14] The immobilization of an EC-specific ligand such as peptide, [15] hepatocyte growth factor, [16] vascular endothelial growth factor [17] and gene delivery [18] onto a biocompatible surface enhances EC selectivity over SMCs and promotes the rapid in situ endothelialization of materials. The peptide sequence Arg-Glu-Asp-Val (REDV) is specifically recognized by the integrin α4β1, which is abundant on ECs and scarce on SMCs.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional copolymer coating of polyethylene glycol, glycidyl methacrylate, and REDV to enhance the selectivity of endothelial cells

Zhang

et al. 2015

Journal of Biomaterials Science, Polymer Edition

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Multifunctional polymer coatings have potential applications in biomaterials. These coatings possess reactive functional groups for the immobilization of specific biological factors that can influence cellular behavior. These coatings also display low nonspecific protein adsorption. In this study, we prepared a multifunctional polymer coating through the deposition of random copolymers of poly(ethylene glycol) methacrylate (PEGMA) and glycidyl methacrylate (GMA) to prevent nonspecific attachment and enable the covalence of Arg-Glu-Asp-Val (REDV) peptide with endothelial cells (ECs) selectivity. Coatings were characterized by X-ray photoelectron spectroscopy (XPS). The adhesion and proliferation of ECs and smooth muscle cells (SMCs) onto the REDV-modified surface were investigated to understand the synergistic action of antifouling PEG and EC selective REDV peptide conjugated GMA. The copolymers containing GMA and PEG groups are very useful as a multifunctional coating material with anti-fouling and ECs specific adhesion for implant materials surface modification.

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Cardiovascular gene delivery: The good road is awaiting☆

Cited by 54 publications

References 230 publications

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

Combinatorial Modification of Degradable Polymers Enables Transfection of Human Cells Comparable to Adenovirus

Multifunctional copolymer coating of polyethylene glycol, glycidyl methacrylate, and REDV to enhance the selectivity of endothelial cells

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