Development of gene transfer for induction of antigen-specific tolerance

Brandon K. Sack, Roland W. Herzog, Cox Terhorst, David M. Markusic

Research output: Contribution to journalReview article

48 Scopus citations

Abstract

Gene replacement therapies, like organ and cell transplantation, are likely to introduce neoantigens that elicit rejection via humoral and/or effector T-cell immune responses. Nonetheless, thanks to an ever-growing body of preclinical studies; it is now well accepted that gene transfer protocols can be specifically designed and optimized for induction of antigen-specific immune tolerance. One approach is to specifically express a gene in a tissue with a tolerogenic microenvironment such as the liver or thymus. Another strategy is to transfer a particular gene into hematopoietic stem cells or immunological precursor cells thus educating the immune system to recognize the therapeutic protein as self. In addition, expression of the therapeutic protein in protolerogenic antigen-presenting cells such as immature dendritic cells and B cells has proven to be promising. All three approaches have successfully prevented unwanted immune responses in preclinical studies aimed at the treatment of inherited protein deficiencies, e.g., lysosomal storage disorders and hemophilia, and of type 1 diabetes and multiple sclerosis. In this review, we focus on current gene transfer protocols that induce tolerance, including gene delivery vehicles and target tissues, and discuss successes and obstacles in different disease models.

Original languageEnglish (US)
Article number14013
Pages (from-to)14013
Number of pages1
JournalMolecular Therapy - Methods and Clinical Development
Volume1
DOIs
StatePublished - Jan 8 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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