Phage display selection of a peptide DNase II inhibitor that enhances gene delivery

Sperinde, Jeffrey J.; Choi, Suk-Jung; Szoka, Francis C.

doi:10.1002/jgm.165

Cited by 37 publications

(15 citation statements)

References 26 publications

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“…27,40 In contrast, the nano-droplet delivery enabled us to establish a direct in vitro selection for the inhibition of DNA nucleases. This selection system affords good enrichment factors (100-500-fold) and good recovery of inhibitorencoding genes (w20%).…”

Section: Discussionmentioning

confidence: 96%

Directed Evolution of Protein Inhibitors of DNA-nucleases by in Vitro Compartmentalization (IVC) and Nano-droplet Delivery

Bernath

Magdassi

Tawfik

2005

Journal of Molecular Biology

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Section: Discussionmentioning

confidence: 96%

Directed Evolution of Protein Inhibitors of DNA-nucleases by in Vitro Compartmentalization (IVC) and Nano-droplet Delivery

Bernath

Magdassi

Tawfik

2005

Journal of Molecular Biology

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“…Studies have also shown the potentially deleterious effects of intracellular endonucleases on transfection efficacy. [17][18][19] Specific inhibitors of pH-sensitive DNases have been shown to enhance cell transfection. 17 Besides confronting lysosomal nucleases, plasmid DNA may also encounter cytosolic nucleases prior to nuclear uptake.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] Specific inhibitors of pH-sensitive DNases have been shown to enhance cell transfection. 17 Besides confronting lysosomal nucleases, plasmid DNA may also encounter cytosolic nucleases prior to nuclear uptake. Based on studies performed in HeLa and COS cells, the estimated half-life of plasmid DNA in cytosolic fluids is approximately 50-90 min.…”

Section: Discussionmentioning

confidence: 99%

Enhanced systemic transgene expression after nonviral salivary gland transfection using a novel endonuclease inhibitor/DNA formulation

Olson

et al. 2003

Gene Ther

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Gene transfer to the major salivary glands is an attractive method for the systemic delivery of therapeutic proteins. To date, nonviral gene transfer to these glands has resulted in inadequate systemic protein concentrations. We believe that identification of the barriers responsible for this inefficient transfection will enable the development of enhanced nonviral gene transfer in salivary glands and other tissues. One potential barrier is the degradation of plasmid DNA by endonucleases. To test this hypothesis, we coadministered two endonuclease inhibitors ((zinc and aurintricarboxylic acid (ATA)) with plasmid DNA, containing the secreted alkaline phosphatase gene (SEAP), to the submandibular glands of rats. The effect of zinc and ATA on SEAP expression, tissue accumulation of plasmid DNA, and plasmid DNA stability was then characterized. We observed that mixtures containing zinc/DNA, ATA/DNA, and zinc/ATA/DNA significantly enhanced both systemic transgene expression and the amount of plasmid DNA associated with treated tissues. The relative endonuclease inhibitory activity of zinc, ATA, and zinc/ATA correlated with the observed effects on transfection efficacy. The use of zinc/ATA enhanced the efficacy of salivary gland transfection by at least 1000-fold versus DNA alone. Importantly, this improved performance resulted in robust systemic secretion of an exogenous protein (SEAP), thus demonstrating the potential this nonviral gene transfer technology has as a method to treat systemic protein deficiencies.

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“…Artificial covalent conjugation combined with phage display are used to display targeting molecules on the surfaces of phages[199–202]. The use of phages, displaying sequences like fibroblast growth factor (FGF)-derived peptides have been proposed to the target cells having the suitable receptors[87, 122, 203, 204]. Increasing the uptake and endosomal release of phages can be accomplished with protein sequences like the “penton base of adenovirus” which facilitates entry and endosomal release[122, 140, 160, 205].…”

Section: Applications Of Targeted Phage-based Nanocarriersmentioning

confidence: 99%

Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos

Karimi

Mirshekari

Basri

et al. 2016

Advanced Drug Delivery Reviews

140

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The main goal of drug delivery systems is to target therapeutic cargoes to desired cells and to ensure their efficient uptake. Recently a number of studies have focused on designing bio-inspired nanocarriers, such as bacteriophages, and synthetic carriers based on the bacteriophage structure Bacteriophages are viruses that specifically recognize their bacterial hosts. They can replicate only inside their host cell and can act as natural gene carriers. Each type of phage has a particular shape, a different capacity for loading cargo, a specific production time, and their own mechanisms of supramolecular assembly, that have enabled them to act as tunable carriers. New phage-based technologies have led to the construction of different peptide libraries, and recognition abilities provided by novel targeting ligands. Phage hybridization with non-organic compounds introduces new properties to phages and could be a suitable strategy for construction of bio-inorganic carriers. In this review we try to cover the major phage species that have been used in drug and gene delivery systems, and the biological application of phages as novel targeting ligands and targeted therapeutics.

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Phage display selection of a peptide DNase II inhibitor that enhances gene delivery

Abstract: A novel peptide DNase II inhibitor has been used to increase transfection. The level of enhancement was found to be significant in multiple cell types with multiple synthetic vectors.

Cited by 37 publications

References 26 publications

Directed Evolution of Protein Inhibitors of DNA-nucleases by in Vitro Compartmentalization (IVC) and Nano-droplet Delivery

Directed Evolution of Protein Inhibitors of DNA-nucleases by in Vitro Compartmentalization (IVC) and Nano-droplet Delivery

Enhanced systemic transgene expression after nonviral salivary gland transfection using a novel endonuclease inhibitor/DNA formulation

Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos

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