Development of gene transfer for induction of antigen-specific tolerance
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050116300638 |
| _version_ | 1828290653346332672 |
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| author | Brandon K Sack Roland W Herzog Cox Terhorst David M Markusic |
| author_facet | Brandon K Sack Roland W Herzog Cox Terhorst David M Markusic |
| author_sort | Brandon K Sack |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T10:39:10Z |
| format | Article |
| id | doaj.art-3c589ab0a9ce47528d80876ecd846c6b |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-13T10:39:10Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-3c589ab0a9ce47528d80876ecd846c6b2022-12-22T02:49:59ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012014-01-011C10.1038/mtm.2014.13Development of gene transfer for induction of antigen-specific toleranceBrandon K Sack0Roland W Herzog1Cox Terhorst2David M Markusic3Seattle Biomedical Research Institute, Seattle, Washington, USADepartment of Pediatrics, University of Florida, Gainesville, Florida, USADivision of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USADepartment of Pediatrics, University of Florida, Gainesville, Florida, USAGene 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.http://www.sciencedirect.com/science/article/pii/S2329050116300638 |
| spellingShingle | Brandon K Sack Roland W Herzog Cox Terhorst David M Markusic Development of gene transfer for induction of antigen-specific tolerance Molecular Therapy: Methods & Clinical Development |
| title | Development of gene transfer for induction of antigen-specific tolerance |
| title_full | Development of gene transfer for induction of antigen-specific tolerance |
| title_fullStr | Development of gene transfer for induction of antigen-specific tolerance |
| title_full_unstemmed | Development of gene transfer for induction of antigen-specific tolerance |
| title_short | Development of gene transfer for induction of antigen-specific tolerance |
| title_sort | development of gene transfer for induction of antigen specific tolerance |
| url | http://www.sciencedirect.com/science/article/pii/S2329050116300638 |
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