Immunology of viral-vector-mediated gene transfer into the brain: an evolutionary and developmental perspective.
The immune system imposes limitations on gene transfer into the brain. Viral vectors injected into the brain's ventricular system elicit innate and adaptive immune responses. However, when injected directly into the brain parenchyma, they elicit only transient inflammation owing to the absence of dendritic cells, which transport antigen to lymph nodes and present it to naive T cells to initiate adaptive immune responses. This article explores the evolutionary and developmental basis of brain immune responses and their implications for viral-vector-mediated neurological gene therapy. Elucidating the cellular and molecular basis of these differential reactions is essential to the long-term success of neurological gene therapy.
Lowenstein
Pedro R
PR
Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Research Pavilion, Room 5093, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. lowensteinp@cshs.org
D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000276:immunology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000276:immunology*; D007107:Immune System / Q000502:physiology*; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology; D010802:Phylogeny; D014780:Viruses / Q000235:genetics*