実質的に自己増殖型mRNA(saRNA)をも含むmRNAワクチン@にDフラグだゾ☆

せっかくボケをかましてあげてるのに誰もツッコミを入れてくれないのでセルフツッコミを入れるゾ☆

2023年12月10日日曜日

シュードウリジンのせいで数十億人が魔改造されちゃったので次はダメもとで天然のウリジン使用のレプリコンプラットフォームだゾ☆

https://jyado.blogspot.com/2023/12/blog-post_10.html

2023年12月9日土曜日

馬鹿根絶ワクチンだゾ☆

https://jyado.blogspot.com/2023/12/blog-post_46.html

2023年12月9日土曜日

シュードウリジンの影響で10回に1回の頻度で起きるｍRNAの誤作動が生み出す魔改造スパイクタンパク質が何の悪影響も及ばさない確率はほぼゼロだゾ☆

https://jyado.blogspot.com/2023/12/101rna.html

2023年12月9日土曜日

最初からmRNAワクチンは『馬鹿を治すワクチン』だったんだゾ☆

https://jyado.blogspot.com/2023/12/mrna_9.html

2023年12月8日金曜日

mRNAワクチン接種は正常に機能してる生命維持OSのDLLに十回に一回はバグるパッチを当てるのと同様の自爆行為だゾ☆

https://jyado.blogspot.com/2023/12/mrna_53.html

2023年12月8日金曜日

ケンブリッジ大学がｍRNAワクチンの必須成分たるシュードウリジンをｍRNAワクチンを欠陥品と至らしめてる原因としダメ出しだゾ☆

https://jyado.blogspot.com/2023/12/rnarna.html

2023年12月8日金曜日

mRNAワクチン接種者の体内に発生するフレームシフト突然変異が今後、齎し得る『謎遺伝子疾患』の一例だゾ☆

https://jyado.blogspot.com/2023/12/mrna_8.html

2023年12月7日木曜日

ｍRNA型接種した勇者はもう全員、欠陥遺伝子組換え人間だゾ☆

https://jyado.blogspot.com/2023/12/rna_7.html

2023年12月7日木曜日

フレームシフトの阻害を利用した新型コロナ治療薬 vs.フレームシフトを誘発するｍRNAワクチン（笑）

https://jyado.blogspot.com/2023/12/vsrna.html

2023年12月7日木曜日

接種したｍRNAの約８％がバグってタンパク質にフレームシフト変異が発生するって事だゾ☆

https://jyado.blogspot.com/2023/12/rna.html 

2023年12月7日木曜日

mRNAワクチンが細胞に作成させるタンパク質の８％はスパイクタンパク以外の『想定外の謎のタンパク質』だゾ☆

https://jyado.blogspot.com/2023/12/mrna.html

肝心の元ネタをちゃんとチェックせんとあかんよ。

N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting
Thomas E. Mulroney,Tuija Pöyry,Juan Carlos Yam-Puc,Maria Rust,Robert F. Harvey,Lajos Kalmar,Emily Horner,Lucy Booth,Alexander P. Ferreira,Mark Stoneley,Ritwick Sawarkar,Alexander J. Mentzer,
Kathryn S. Lilley,C. Mark Smales,Tobias von der Haar,Lance Turtle,Susanna Dunachie,
Paul Klenerman,James E. D. Thaventhiran &Anne E. Willis

Nature (2023)

Abstract

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2. 

Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3,4,5, but their effects on mRNA translation fidelity have not been fully explored. 

Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination. 

The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. 

However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products. 

Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization.

https://www.nature.com/articles/s41586-023-06800-3

◯　The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling

☓　The +1 ribosome frameshifting observed is the consequence of N1-methylpseudouridine-induced ribosome stalling

更に…

It was unclear whether 1-methylΨ affected mRNA decoding rates, or another process, during elongation. We reasoned that slower decoding of 1-methylΨ codons during translation elongation could lead to ribosome stalling, similar to previous observations for ‘hungry’ codons at sites of +1 frameshifting during translation of naturally occurring mRNA21,28.

https://www.nature.com/articles/s41586-023-06800-3

そして、

Conclusions

We show that 1-methylΨ is a modified ribonucleotide that significantly increases +1 ribosomal frameshifting during mRNA translation and that cellular immunity to +1 frameshifted products can occur following vaccination with mRNA containing 1-methylΨ. To our knowledge, this is the first report that mRNA modification affects ribosomal frameshifting. Alongside this impact on host T cell immunity, the off-target effects of ribosomal frameshifting could include increased production of new B cell antigens. Other ribonucleotide modification strategies, such as incorporation of 5-methoxyU, significantly decreased translation efficiency of IVT mRNAs, which may limit clinical translation. Although we have shown that translation of N1-methylpseudouridylated mRNA leads to +1 ribosomal frameshifting in vitro and in cultured cells, it is conceivable that other mistranslation events (such as leaky scanning) could also contribute to T cell responses to +1 frameshifted peptide antigens. We show that IVT mRNAs contain few nucleotide insertions and deletions, and this is not changed by 1-methylΨ incorporation. Our data show that +1 ribosomal frameshifting occurs at two characterized slippery sequences. Therefore, we believe that the minor band of approximately 50 kDa produced by Fluc+1FS mRNA translation is probably a consequence of several frameshifting events (Fig. 1e). Translation of mRNA containing 1-methylΨ leads to slower translation elongation, caused by altered aminoacyl-tRNA binding, which demonstrates why +1 ribosomal frameshifting does not occur during unmodified mRNA translation—both ribosome stalling and ribosome slippery sequences seem to be required for productive +1 ribosome frameshifting. Our mechanistic data are supported by previous observations of ribosomal frameshifting during translation of naturally occurring mRNAs, which implicate ribosome stalling and require ribosome slippery sequences for +1 frameshifting21,26,27,28,33,34. These findings are of particular importance to our fundamental understanding of how ribonucleotide modification affects mRNA translation, and for designing and optimizing future mRNA-based therapeutics to avoid mistranslation events that may decrease efficacy or increase toxicity.

https://www.nature.com/articles/s41586-023-06800-3

◯　We show that 1-methylΨ is a modified ribonucleotide that significantly increases +1 ribosomal frameshifting 

☓　We show that 1-methylΨ is a modified ribonucleotide that causes +1 ribosomal frameshifting

要するに…

フレームシフト変異の主な原因が主なシュードウリジンとは断言してないんですよ。

要するに、肝心のフレームシフト変異の原因は別にあり、それはまだ特定されておらず、シュードウリジンがフレームシフト変異の頻度を増やすという事が分かったって話なんですよ。

要するに…

数十億人に接種しちゃったmRNAワクチンが想定外の免疫反応を起こし始めちゃったのでとりあえずシュードウリジンのせいにして誤魔化そうって話。

だから…

天然のウリジン使用のレプリコンプラットフォーム、要するに自己増殖型mRNA(saRNA)でもフレームシフト変異、またはその他の想定外の有害な変異が起きない保証なんてないのですよ。

2023年12月9日土曜日

mRNAで細胞に何の弊害もなくスパイクタンパク質を作らせるなんて芸当は不可能なんですよ

https://jyado.blogspot.com/2023/12/mrna_21.html

あ、それと…　

自己増殖型mRNA(saRNA)、要するにレプリコンも筋肉注射か静脈注射とかで直接体内に打ち込まないかぎり大丈夫ですので未接種者の皆様はシェディングサマナにご用心。

、、、（爆ｗｗｗｗｗｗｗｗｗｗ