Low efficacy of recombinant SV40 in Ugt1a1-/- mice with severe inherited hyperbilirubinemia

In contrast to AAV, Simian Virus 40 (rSV40) not inducing neutralizing antibodies (NAbs) allowing re-treatment seems a promising vector for neonatal treatment of inherited liver disorders. Several studies have reported efficacy of rSV40 in animal models for inherited liver diseases. In all studies th...

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Published in:PloS one 2021-01, Vol.16 (4), p.e0250605-e0250605
Main Authors: Shi, Xiaoxia, Bortolussi, Giulia, Bloemendaal, Lysbeth Ten, Duijst, Suzanne, Muro, Andrés F, Bosma, Piter J
Format: Article
Language:English
Subjects:
Aggressive behavior
Antibodies
Antigens
Appetite loss
Bilirubin
Biology and life sciences
Biotechnology
Body weight
Body weight loss
Brain damage
Brain research
Conjugation
Crigler-Najjar syndrome
Editing
Enzymes
Gene therapy
Genetic engineering
Hyperbilirubinemia
Intestine
Light therapy
Lipophilic
Liver
Medical research
Medicine and Health Sciences
mRNA
Nanoparticles
Production methods
Recombinase
Research and Analysis Methods
Reviews
Stereotyped behavior
Transfection
Transplants & implants
Vectors (Biology)
Weight loss
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Bortolussi, Giulia
Bloemendaal, Lysbeth Ten
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Bosma, Piter J
description In contrast to AAV, Simian Virus 40 (rSV40) not inducing neutralizing antibodies (NAbs) allowing re-treatment seems a promising vector for neonatal treatment of inherited liver disorders. Several studies have reported efficacy of rSV40 in animal models for inherited liver diseases. In all studies the ubiquitous endogenous early promoter controlled transgene expression establishing expression in all transduced tissues. Restricting this expression to the target tissues reduces the risk of immune response to the therapeutic gene. In this study a liver specific rSV40 vector was generated by inserting a hepatocyte specific promoter. This increased the specificity of the expression of hUGT1A1 in vitro. However, in vivo the efficacy of rSV40 appeared too low to demonstrate tissue specificity while increasing the vector dose was not possible because of toxicity. In contrast to earlier studies, neutralizing antibodies were induced. Overall, the lack of a platform to produce high titered and pure rSV40 particles and the induction of NAbs, renders it a poor candidate for in vivo gene therapy.
doi_str_mv 10.1371/journal.pone.0250605
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subjects Aggressive behavior
Antibodies
Antigens
Appetite loss
Bilirubin
Biology and life sciences
Biotechnology
Body weight
Body weight loss
Brain damage
Brain research
Conjugation
Crigler-Najjar syndrome
Editing
Enzymes
Gene therapy
Genetic engineering
Hyperbilirubinemia
Intestine
Light therapy
Lipophilic
Liver
Medical research
Medicine and Health Sciences
mRNA
Nanoparticles
Production methods
Recombinase
Research and Analysis Methods
Reviews
Stereotyped behavior
Transfection
Transplants & implants
Vectors (Biology)
Weight loss
title Low efficacy of recombinant SV40 in Ugt1a1-/- mice with severe inherited hyperbilirubinemia
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