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Adenovirus Vector-Derived VA-RNA-Mediated Innate Immune Responses.
- Source :
- Pharmaceutics; Sep2011, Vol. 3 Issue 3, p338-353, 16p, 3 Diagrams
- Publication Year :
- 2011
-
Abstract
- The major limitation of the clinical use of replication-incompetent adenovirus (Ad) vectors is the interference by innate immune responses, including induction of inflammatory cytokines and interferons (IFN), following in vivo application of Ad vectors. Ad vector-induced production of inflammatory cytokines and IFNs also results in severe organ damage and efficient induction of acquired immune responses against Ad proteins and transgene products. Ad vector-induced innate immune responses are triggered by the recognition of Ad components by pattern recognition receptors (PRRs). In order to reduce the side effects by Ad vector-induced innate immune responses and to develop safer Ad vectors, it is crucial to clarify which PRRs and which Ad components are involved in Ad vector-induced innate immune responses. Our group previously demonstrated that myeloid differentiating factor 88 (MyD88) and toll-like receptor 9 (TLR9) play crucial roles in the Ad vector-induced inflammatory cytokine production in mouse bone marrow-derived dendritic cells. Furthermore, our group recently found that virus associated-RNAs (VA-RNAs), which are about 160 nucleotide-long non-coding small RNAs encoded in the Ad genome, are involved in IFN production through the IFN-β promoter stimulator-1 (IPS-1)-mediated signaling pathway following Ad vector transduction. The aim of this review is to highlight the Ad vector-induced innate immune responses following transduction, especially VA-RNA-mediated innate immune responses. Our findings on the mechanism of Ad vector-induced innate immune responses should make an important contribution to the development of safer Ad vectors, such as an Ad vector lacking expression of VA-RNAs. [ABSTRACT FROM AUTHOR]
- Subjects :
- ADENOVIRUSES
RNA
NATURAL immunity
IMMUNE response
CYTOKINES
INTERFERONS
GENE therapy
Subjects
Details
- Language :
- English
- ISSN :
- 19994923
- Volume :
- 3
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 66649870
- Full Text :
- https://doi.org/10.3390/pharmaceutics3030338