Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How?

Sharma, Ashish Ranjan; Kundu, Shyamal Kumar; Nam, Ju-Suk; Sharma, Garima; Doss, C. George Priya; Lee, Sang-Soo; Chakraborty, Chiranjib

doi:10.1155/2014/327950

Cited by 34 publications

(26 citation statements)

References 126 publications

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“…Recent findings have indicated that proteins from the Rspondin (Rspo) family are important Wnt pathway activators [132]. Accordingly, conditional deletion of Rspo3 in mice abrogates proper perivenous zonation.…”

Section: Beta-catenin and Zonationmentioning

confidence: 99%

Metabolic zonation of the liver: The oxygen gradient revisited

2017

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The liver has a multitude of functions which are necessary to maintain whole body homeostasis. This requires that various metabolic pathways can run in parallel in the most efficient manner and that futile cycles are kept to a minimum. To a large extent this is achieved due to a functional specialization of the liver parenchyma known as metabolic zonation which is often lost in liver diseases. Although this phenomenon is known for about 40 years, the underlying regulatory pathways are not yet fully elucidated. The physiologically occurring oxygen gradient was considered to be crucial for the appearance of zonation; however, a number of reports during the last decade indicating that β-catenin signaling, and the hedgehog (Hh) pathway contribute to metabolic zonation may have shifted this view. In the current review we connect these new observations with the concept that the oxygen gradient within the liver acinus is a regulator of zonation. This is underlined by a number of facts showing that the β-catenin and the Hh pathway can be modulated by the hypoxia signaling system and the hypoxia-inducible transcription factors (HIFs). Altogether, we provide a view by which the dynamic interplay between all these pathways can drive liver zonation and thus contribute to its physiological function.

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Section: Beta-catenin and Zonationmentioning

confidence: 99%

Metabolic zonation of the liver: The oxygen gradient revisited

2017

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“…Protein biopharmaceuticals have many advantages over other drugs; for example, they are highly specific, well-tolerated by the body, and eliminate the need for gene therapy2. However, formation of aggregates during drug administration causes proteins to lose their activity over time and may also trigger potentially dangerous immune responses3.…”

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confidence: 99%

Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels

Rajan

Matsumura

2017

Sci Rep

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Protein aggregation is a process by which misfolded proteins polymerizes into aggregates and forms fibrous structures with a β-sheet conformation, known as amyloids. It is an undesired outcome, as it not only causes numerous neurodegenerative diseases, but is also a major deterrent in the development of protein biopharmaceuticals. Here, we report a rational design for the synthesis of novel zwitterionic polymer-based core-shell nanogels via controlled radical polymerization. Nanogels with different sizes and functionalities in the core and shell were prepared. The nanogels exhibit remarkable efficiency in the protection of lysozyme against aggregation. Addition of nanogels suppresses the formation of toxic fibrils and also enables lysozyme to retain its enzymatic activity. Increasing the molecular weight and degree of hydrophobicity markedly increases its overall efficiency. Investigation of higher order structures revealed that lysozyme when heated without any additive loses its secondary structure and transforms into a random coil conformation. In contrast, presence of nanogels facilitates the retention of higher order structures by acting as molecular chaperones, thereby reducing molecular collisions. The present study is the first to show that it is possible to design zwitterionic nanogels using appropriate polymerization techniques that will protect proteins under conditions of extreme stress and inhibit aggregation.

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“…Nonviral-based delivery systems include cationic liposome, PEGylated system, HESylated system, and nanoparticle-based delivery system. 24 Viral vectors have a high transduction efficiency, but are safety concerned due to systemic toxicity and the immunogenicity induced in the host. Nonviral vectors have the advantages of nonimmunogenic, available to production on large scale and easy modification, but the transduction efficiency is relatively low.…”

Section: Discussionmentioning

confidence: 99%

Enhanced EJ Cell Killing of ¹²⁵I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter

Zhang

Liu

et al. 2015

Cancer Biotherapy and Radiopharmaceuticals

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Aim: To investigate the enhancing effect of radionuclide therapy by the therapeutic gene placed under the control of radio-responsive promoter.Methods: The recombinant lentivirus E8-codA-GFP, including a synthetic radiation-sensitive promoter E8, cytosine deaminase (CD) gene, and green fluorescent protein gene, was constructed. The gene expression activated by 125I radiation was assessed by observation of green fluorescence. The ability of converting 5-fluorocytosine (5-FC) to 5-fluorourial (5-FU) by CD enzyme was assessed by high-performance liquid chromatography. The viability of the infected cells exposed to 125I in the presence of 5-FC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the infected cells exposed to 125I alone served as negative control and 5-FU as positive control.Results: The recombinant lentiviral vector was constructed successfully. On exposure of infected cells to 125I, green fluorescence can be observed and 5-FU can be detected. MTT assay showed that the survival rate for infected cells treated with 125I was lower compared with the 125I control group, but higher than the positive control group.Conclusion: The synthetic promoter E8 can induce the expression of downstream CD gene under 125I radiation, and the tumor killing effect of 125I can be enhanced by combining CD gene therapy with radiosensitive promoter.

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Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How?

Cited by 34 publications

References 126 publications

Metabolic zonation of the liver: The oxygen gradient revisited

Metabolic zonation of the liver: The oxygen gradient revisited

Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels

Enhanced EJ Cell Killing of ¹²⁵I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter

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Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How?

Cited by 34 publications

References 126 publications

Metabolic zonation of the liver: The oxygen gradient revisited

Metabolic zonation of the liver: The oxygen gradient revisited

Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels

Enhanced EJ Cell Killing of 125I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter

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Product

Resources

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Enhanced EJ Cell Killing of ¹²⁵I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter