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Recent Advances in Understanding of the Immunological Off-target Effects of siRNA.
MedLine Citation:
PMID:  22023470     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Short interfering RNAs (siRNAs) are the most commonly used RNA interference (RNAi) triggers. They hold promise as potent therapeutic tools, as demonstrated by recent successful in vivo experiments. However, in addition to triggering intended sequence-specific silencing effects, the reagents of RNAi technology can often cause side effects, including immunological off-target effects. The cellular sensors of foreign RNA, such as RIG-I or Toll-like receptors, involved in innate immune antiviral responses, are activated by RNAi reagents. Stimulation of these pathways results in changes in the cellular transcriptome and proteome that can lead to the inhibition of cell division and growth and eventually apoptosis. An additional undesired effect in the context of research applications may be the misinterpretation of experimental results. To date, a number of the specific features of siRNA structure, sequence and delivery mode that are responsible for these effects have been identified. This knowledge may be helpful in designing safer gene-silencing reagents. In this article we discuss the recent developments in the field of non-specific toxic effects caused by RNAi triggers and their delivery vehicles. These data are critically discussed and evaluated, taking advantage of relevant information compiled in the recently launched RNAimmuno database (http://rnaimmuno.ibch.poznan.pl).
Authors:
Marta Olejniczak; Katarzyna Polak; Paulina Galka-Marciniak; Wlodzimierz J Krzyzosiak
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-21
Journal Detail:
Title:  Current gene therapy     Volume:  11     ISSN:  1875-5631     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101125446     Medline TA:  Curr Gene Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Cancer Genetics Institute of Bioorganic Chemistry Polish Academy of Sciences Noskowskiego 12/14, 61-704 Poznan Poland. wlodkrzy@ibch.poznan.pl.
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