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Transgene expression restricted for the target tissue by using tissue particular promoters has been extensively exploited to avoid immune responses for the transgene.

Thus the use of muscle particular promoters would not protect against immune responses if cross priming is involved, even when the vectors tend not to transduce APCs. That being mentioned, it truly is nevertheless preferable to avoid expressing in APCs as direct transduction of APCs can exacerbate immune responses. It really should be noted that there happen to be some examples of tolerance induction Cabozantinib by expressing peptide immunoglobulin fusion proteins in B cells. The exact mechanism of this tolerance induction is unclear, however it appears to involve T regulatory epitopes encoded in the immunoglobulin G molecule. The liver is an attractive target for gene transfer as it has long been known as tolerogenic organ. Studies in mice have shown that tolerance induction by liver specific expression of the transgene is an active suppresive mechanism involving the induction of Treg cells.

They have shown the incorporation of the microRNA mir 142 3p target sequence suppresses the expression of the transgene in hematopoietic lineages, thus avoiding neutralizing antibodies against the transgene NSCLC product. Similar studies have been carried out using hydrodynamic delivery of plasmid under the control of tissue specific promoters and mir 142 3p. Although incorporation of the microRNA sequence did decrease antitransgene antibody titers, transgene specific immune tolerance was not achieved. Therefore, in some systems the use of tissuespecific promoters will be enough to avoid immune responses, whereas in a different context additional strategies may be required. Regulated expression of the transgene is another strategy that can be used to minimize the risk of unwanted immune responses.

Delivering vector to tissue and/or a space considered to be immune Cabozantinib privileged is a logical option to evade unwanted immune responses in gene therapy. These areas include the brain, eye, testis, and uterus among others.