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28.Apr.09 2009Sequences derived from self-RNA containing certain natural modifications act as suppressors of RNA-mediated inflammatory immune response

Hier ein toller Artikel, der zeigt, das nur zwei kleinen Modifikationen auf einer RNA darüber entscheiden, ob die RNA vom Immunesystem erkannt wird oder nicht. GVOs mit zahlreichen neuen synthetischen RNA können das Immunsystem ziemlich belasten.

International Immunology Advance Access published online on March 30, 2009 International Immunology, doi:10.1093/intimm/dxp030 http://intimm.oxfordjournals.org/cgi/content/short/dxp030v1 Sequences derived from self-RNA containing certain natural modifications act as suppressors of RNA-mediated inflammatory immune responses Sibylle Tluk1, Marion Jurk1, Alexandra Forsbach1, Risini Weeratna2, Ulrike Samulowitz1, Arthur M. Krieg3, Stefan Bauer4 and Jörg Vollmer1 1 Coley Pharmaceutical GmbH—A Pfizer Company, Merowingerplatz 1a, 40225 Düsseldorf, Germany 2 Pfizer Vaccine Ottawa, 340 Terry Fox Drive, Suite 200, Kanata (Ottawa), Ontario K2K 3A2, Canada 3 Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA 4 Institute for Immunology, Biomedizinisches Forschwngszentrum, Philipps University Marburg, Hans-Meerwein-Strasse 2, 35043 Marburg, Germany Correspondence to: Correspondence to: J. Vollmer; E-mail: joerg.vollmer@pfizer.com The ability of the host to distinguish between self and foreign nucleic acids is one of the critical factors contributing to the recognition of pathogens by Toll-like receptors (TLRs). Under certain circumstances, eukaryotic self-RNA may reach TLR-containing compartments allowing for self-recognition. Specific modifications were previously demonstrated to suppress immune activation when placed at several positions in an immune stimulatory RNA or silencing RNA (siRNA). However, we show that even a simple natural modification such as a single 2'-O-methylation at different nucleotide positions throughout a sequence derived from a self-RNA strongly interferes with TLR-mediated effects. Such a single modification can even have an inhibitory effect in vitro and in vivo when placed in a different than the immune stimulatory RNA strand acting as suppressive RNA. Several safeguard mechanisms appear to have evolved to avoid cellular TLR-mediated activation by self-RNAs that may under other circumstances result in inflammatory or autoimmune responses. This knowledge can be used to include as few as a single 2'-O-methyl modification at a specific position in a siRNA sense or anti-sense strand to avoid TLR immune effects.

02.Apr.06 Prescott et al 2005:Transgenic Expression of Bean r-Amylase Inhibitor in Peas Results in Altered Structure and Immunogenicity

An unexpected finding of allergenicity of a GM pea which would not have been picked up by the current pratice of allergenicity testing by the EFSA during the routine approval process.

This paper makes clear that a improvement of the risk assessment carried out by the EFSA is overdue.

02.Apr.06 Spoek et al 2005: Suggestions for the Assessment of the Allergenic Potential of Genetically Modified Organisms

The current approach to assess the allergenicity potential of GMOs undertaken by EFSA (European Food Safety Agency) is not state of the. Speoke a et al propose a more stringent mehtod to assess the potential of allergenicty of GMOs.

02.Apr.06 Mazza et al 2005: Assessing the transfer of genetically modified DNA from feed to animal tissues

Detection of synthetic GMO fragments in the blood of pigs

22.Okt.05 Waterland, Jirtle 2003: Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation

This article is a breka through in food sciene, and shows that food what the mother eats can influence the size and colour of mice. On this article the New Scientist jounrla concluded You are what your mother ate.

This article demonstrates that the function of the genome and the interaction with the fodd or environemt is really not well understood. Therefore genetically modified food or feed shall not be approved for human consumption until all mystereis on the genome are resolved

26.Jul.05 Rang et al 2005: Detection of RNA variants transcribed from the transgene in Roundup Ready soybean

Our data demonstrate that at least 150 bp of this DNA region are transcribed in Roundup Ready soybean.

Abstract The acreage for genetically modified crops (GMOs)—particularly soybean—has steadily increased since 1996, when the first crop of Roundup Ready soybean (intended for food production) was grown. The Roundup Ready soybean varieties derive from a soybean line into which a glyphosate-resistant enolpyruvylshikimate- 3-phosphate-synthase (EPSPS) gene was introduced. The inserted and the flanking regions in Roundup Ready soybean have recently been characterized. It was shown that a further 250-bp fragment of the epsps gene is localized downstream of the introduced nos terminator of transcription, derived from the nopaline synthase gene from Agrobacterium tumefaciens. We examined whether this 250-bp fragment could be of functional importance. Our data demonstrate that at least 150 bp of this DNA region are transcribed in Roundup Ready soybean. Transcription of the fragment depends on whether readthrough events ignore the nos terminator signal located upstream. Our data also indicate that the read-through product is further processed, resulting in four different RNA variants from which the transcribed region of the nos terminator is completely deleted. Deletion results in the generation of open reading frames which might code for (as yet unknown) EPSPS fusion proteins. The nos terminator is used as a regulatory element in several other GMOs used for food production. This implies that read through products and transcription of RNA variants might be a common feature in these GMOs.

25.Jul.04 Vecchio et al 2004: Ultrastructural analysis of testes from mice fed on genetically modifed soybean

Efects of GM soeybean on testis of mice in an 8 months feeding trial

21.Dez.03 Gibbs 2003: The unseen genome. Gems among the junk

Quite important and good article on the role of so called junk DNA. Scientist had believed that 98 % of the human DNA are junk. This review shows that this will go down as one of the biggest mistakes int the hsitory of molecular biology.

This article is confirmed by more and more data see for example the issue No 5740 Volume 309 of the Journal "Science" Mapping RNA Form and Function from 2 Spetmeber 2005 http://www.sciencemag.org/content/vol309/issue5740/index.shtml

21.Okt.03 Malatesta et al 2002: Ultrastructural Morphometrical and Immunocytochemical Analyses of Hepatocyte Nuclei from Mice Fed on GM Soybean

One of the few independent food safety studies of GM-soybeans detected changes in the cell structure and function in an 8 mo

22.Okt.02 Tsui et al 2002: Stability of Endogenous and Added RNA in Blood Specimens, Serum, and Plasma

A further article which shows that RNA is remarkable stalbe in the blood. Most scientis believed that RNA is degraded in seconds when administerred into the blood because of ubiquitous RNAse enzymes

On that bases any harm of RNA by GMOs was generally excluded. THis and other articles proves that this assumptions was premature. And probably we will get more surprises int the world of Fodd Rna which is currently out of scope of any research programm in the risk assessment of GMOs

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