Transgene expression restricted for the target tissue by utilizing tissue specific promoters continues to be extensively exploited to avoid immune responses for the transgene.
As a result the usage of muscle specific promoters would not protect against immune responses if cross priming is involved, even if the vectors don't transduce APCs. That currently being mentioned, it really is still preferable to avoid expressing in APCs as direct transduction of APCs can exacerbate immune responses. It need to be noted that there have already been 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.
Lowenstein et al. reviewed a series of studies on viral vector delivery into the brain of naive and previously vectorimmunized animal models demonstrate that the immunologic protection of the naive brain could be hampered by the local of the injection, vector dose and vector type. Thus, it is likely that perturbations of the immune privileged sites may compromise the anatomical integrity of these natural barriers and change local immune responses.
Monday, March 18, 2013
Tips On How To End Up Getting Excellent At Cabozantinib Capecitabine
Subscribe to:
Post Comments (Atom)
No comments:
Post a Comment