Internalizing Antibody-Based Targeted Gene Delivery for Human Cancer Cells

Shiota, Maki; Ikeda, Yutaka; Kaul, Zeenia; Itadani, Jun; Kaul, Sunil C.; Wadhwa, Renu

doi:10.1089/hum.2007.087

Cited by 20 publications

(15 citation statements)

References 33 publications

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“…It is envisioned that mortalin may also be explored in future for inducing protective immunity, primarily in modulating host immunity to tumors and infectious pathogens. Antibodies raised against mortalin have seen to get internalized in tumor cells [125,126].…”

Section: Anti-mortalin Based Immunotherapiesmentioning

confidence: 99%

The Versatile Stress Protein Mortalin as a Chaperone Therapeutic Agent

Deocaris

Kaul²,

Wadhwa³

2009

PPL

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Age- and stress-induced modulations in chaperone systems result in "chaperono-deficiency" or "chaperon-opulence". Development of modulators, of chaperone function has therefore, become an emerging field in drug development and discovery. This mini-review summarizes (i) the events leading to identification of an Hsp70 family stress chaperone, mortalin, (ii) experimental evidence to its role in old age diseases and cancer, and (iii) proposes it as a chaperono-therapeutic agent. As post-translational modifications and expression changes in mortalin are being explored as a biomarker for cancer, cardiovascular diseases and neurodegeneration, we discuss here how the current tools used in studying mortalin (e.g. antibodies, peptides, ribozymes, antisense and siRNA, recombinant proteins and small molecules etc.) could be creatively applied in a clinical setting to manage stress and to treat various chaperone-based maladies or "chaperonopathies".

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Section: Anti-mortalin Based Immunotherapiesmentioning

confidence: 99%

The Versatile Stress Protein Mortalin as a Chaperone Therapeutic Agent

Deocaris

Kaul²,

Wadhwa³

2009

PPL

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“…Recent studies have suggested that some duplex siRNA sequences have off-target effects and toxicities associated with immune stimulation [21,30,31]. There has been considerable controversy over the potential of siRNA-induced interferon response.…”

Section: Resultsmentioning

confidence: 99%

Cardiomyocyte-targeted siRNA delivery by prostaglandin E2-Fas siRNA polyplexes formulated with reducible poly(amido amine) for preventing cardiomyocyte apoptosis

Kim¹,

Jeong²,

Ou³

et al. 2008

Biomaterials

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A cardiomyocyte-targeted Fas siRNA delivery system was developed using prostaglandin E 2 (PGE 2 )-modified siRNA polyplexes formed by a reducible poly(amido amine) to inhibit cardiomyocyte apoptosis. PGE 2 , which was used as a specific ligand for cardiomyocyte targeting, was conjugated to the terminal-end of the sense siRNA (PGE 2 -siRNA). The reducible cationic copolymer, synthesized via Michael-type polyaddition of 1,6-diaminohexane and cystamine bisacrylamide (poly(DAH/CBA)), tightly condensed the PGE 2 -siRNA conjugate to form nanosize polyplexes having a diameter of 100-150 nm. The PGE 2 -siRNA/poly(DAH/CBA) polyplexes decomplexed to release PGE 2 -siRNA in a cytosolic reducing environment due to the degradation of the reducible poly(DAH/CBA). The cellular uptake of the PGE 2 -siRNA/poly(DAH/CBA) polyplex was increased in rat cardiomyocytes (H9C2 cells) due to PGE 2 receptor-mediated endocytosis. When H9C2 cells were transfected with siRNA against Fas, a key regulator of ischemia-induced apoptosis, the PGE 2 -Fas siRNA/poly(DAH/CBA) polyplex delivery system led to a significant increase in Fas gene silencing, resulting in inhibition of cardiomyocyte apoptosis. The PGE 2 -Fas siRNA/poly(DAH/ CBA) polyplex did not induce interferon-alpha in peripheral blood mononuclear cells. These results suggest that the PGE 2 -Fas siRNA/poly(DAH/CBA) polyplex formulation may be clinically applicable as a cardiomyocyte-targeted Fas siRNA delivery system to inhibit apoptosis in cardiovascular disease.

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“…Anti-mortalin monoclonal mouse antibody (Mot-mAb) was prepared as described earlier [33]. Full-length His-tagged recombinant mortalin protein was used as an antigen for raising polyclonal and monoclonal antibodies by standard protocols.…”

Section: Methodsmentioning

confidence: 99%

Express ELISA for Detection of Mortalin

Garg

Ohmiya

et al. 2019

BioTechniques

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Mortalin is a widely studied stress chaperone that plays a significant role in diseases such as cancer, diabetes mellitus, liver cirrhosis, neurodegeneration and generalized aging. Based on these, the level of mortalin expression has been predicted to be an important and valuable diagnostic and prognostic marker. Conventional methods of protein analyses, such as Western blotting, immunohistochemistry or ELISA with antibodies provide specific, sensitive and useful outcomes. However, they are limited by lengthy and time-consuming protocols. Here, we present an upgrade to the existing ELISA techniques. We have prepared a conjugate of anti-mortalin antibody and luciferase enzyme that can be recruited for rapid (∼3 h) and quantitative detection of mortalin expression in a given biological sample.

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Internalizing Antibody-Based Targeted Gene Delivery for Human Cancer Cells

Cited by 20 publications

References 33 publications

The Versatile Stress Protein Mortalin as a Chaperone Therapeutic Agent

The Versatile Stress Protein Mortalin as a Chaperone Therapeutic Agent

Cardiomyocyte-targeted siRNA delivery by prostaglandin E2-Fas siRNA polyplexes formulated with reducible poly(amido amine) for preventing cardiomyocyte apoptosis

Express ELISA for Detection of Mortalin

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