APC-mediated tolerance induction for therapy of multiple sclerosis

A multiple sclerosis and protein technology, applied in gene therapy, medical raw materials derived from mammals, medical raw materials derived from viruses/bacteriophages, etc., can solve problems such as adverse side effects

Inactive Publication Date: 2014-08-27
苏黎世大学数学和自然科学部
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These investigators used a constitutive promoter that mediates MOG expression in different hematopoietic cells, which can cause unwanted side effects

Method used

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  • APC-mediated tolerance induction for therapy of multiple sclerosis
  • APC-mediated tolerance induction for therapy of multiple sclerosis
  • APC-mediated tolerance induction for therapy of multiple sclerosis

Examples

Experimental program
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Embodiment Construction

[0016] The present invention is based on the surprising discovery that expression of a transgene encoding an autoantigen in dendritic cells driven by a dendritic cell-specific promoter sequence not only prevents the onset of autoimmune disease but also reverses established autoimmunity process and halt the development of demyelinating disease.

[0017] The present invention demonstrates that ex vivo engineering of hematopoietic stem cells (HSCs) with vectors expressing antigens involved in MS from dendritic cell-specific promoters induces permanent antigen-specific tolerance.

[0018] According to the present invention, there is provided an expressed nucleic acid sequence encoding a human autoantigen under the transcriptional control of a dendritic cell-specific promoter.

[0019] In the context of the present invention, a DC-specific promoter sequence is a nucleic acid sequence under whose control a coding sequence is constitutively expressed in human immature dendritic cells...

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Abstract

The invention relates to transgene expression constructs—particularly self inactivating lentiviral vectors—comprising a dendritic cell specific promoter controlling the expression of autoantigen proteins, namely myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein, for use in the therapy of multiple sclerosis.

Description

Background technique [0001] The causes of multiple sclerosis (MS or disseminated encephalomyelitis) are not well understood and the pathogenic processes leading to the disease are not fully understood. Current knowledge supports the pathogenesis of T cell-mediated autoimmunity targeting myelin components or myelin-producing cells. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are characterized by the activation and accumulation of antigen-presenting cells (APCs) and autoreactive lymphocytes within the central nervous system (CNS). Some of the myelin proteins known to be recognized by autoreactive T cells include myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). [0002] Myelin basic protein (MBP) is a major component of the myelin sheath of oligodendrocytes and Schwann cells. The genetic data of its human orthologue is publicly available at the US National Center for Biotechnology Information (NCB...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00
CPCA61K35/12A61K48/0058A61K35/76C12N2830/008A61K31/10C12N15/11A61P25/00A61P37/00A61P43/00
Inventor C·德雷施B·戴安德雷德佩雷拉M·阿克曼C·法拉艾费尔
Owner 苏黎世大学数学和自然科学部
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