Immune responses to replication-defective HSV-1 type vectors within the CNS: implications for gene therapy

Characterisation of systemic dissemination of nonreplicating adenoviral vectors from tumours in local gene delivery

“…The most widely used vectors for gene delivery are genetically engineered viruses, because they, in the long-term evolution of nature, are equipped with specific machineries that facilitate DNA transport into the nucleus of cells (Baranowski et al, 2001). However, a main drawback of viral vectors is the toxicity caused by undesirable acute immune response to viral proteins (Brown and Lillicrap, 2002;Bowers et al, 2003;Chen et al, 2003;Jooss and Chirmule, 2003;Lowenstein, 2003). Moreover, proteins from transgene expression may also exert adverse effects on normal cells either directly or indirectly through conversion of prodrugs to cytotoxic agents (Freeman et al, 1993;Rosenfeld et al, 1995;Alvarez and Curiel, 1997;Pope et al, 1997;Chada et al, 2003).…”

Evolving gene therapy approaches for osteosarcoma using viral vectors: Review

“…In addition, the cellular immune response, mediated through adenoviral specific CD8 positive T cells, eliminate the cells' expressing viral and transgene products (24). Overall the undesirable acute immune response to viral proteins was considered the main drawback of virus-based gene therapy (13,14,16).…”

Virology and immunology of gene therapy, or virology and immunology of high MOI infection with defective viruses

“…The only viral nucleic acid remaining represents sequences required for genome replication and packaging into virions. 5,6 Further, capsids have been engineered to reduce viron binding to endogenous viral receptors, and to retarget infection of predetermined cell types. 7 Transcriptional regulatory systems facilitate directed expression of transgenes in a cell-type-specific fashion.…”

“…Especially, this issue surveys the inflammatory and immune responses to HSV-1 vectors, 5 AAV-vectors, 9,10 adenovirus vectors, 6,9,11 and further investigates how different arms of the immune response affect both replication-defective 5,6,9 and replication-competent vectors. 5,12,13 Of further importance to the field, this issue explores how inflammatory and immune responses will vary, even for the same vector, depending on the target organ being injected and transduced. 6,11,13 Thus, this special issue examines immune responses to vectors infecting different tissues, that is, muscle, 9 liver, 10 eye, 11 and brain.…”