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☆

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☆

The researchers found that mRNAs containing the form of pseudouridine used in Pfizer’s and Moderna’s COVID-19 vaccines were much more likely to induce frameshifted proteins than mRNAs with normal uridines. In their experiments, roughly 8% of the proteins produced from their experimental mRNAs were frameshifted.

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

フレームシフト突然変異
英語: frame shift mutation
ドイツ語: Rastermutation

遺伝学。コードする配列上で、正確な3の倍数ではない個数のヌクレオチドの挿入または欠失が起こることにより生じる突然変異。このような変化が起きた点から先は、コドン（三つの塩基の配列）は読み枠を外れて読まれる。すなわち、遺伝子を読み取るフレームが変わるため、完全に異なるアミノ酸のセットでタンパク質が作られる。
分類: 突然変異、
関連語: 遺伝子突然変異、突然変異誘発、先祖返り
復帰突然変異体、致死突然変異
染色体異常、突然変異原
塩基対置換

 

A frameshift mutation in a gene refers to the insertion or deletion of nucleotide bases in numbers that are not multiples of three. This is important because a cell reads a gene’s code in groups of three bases when making a protein. Each of these “triplet codons” corresponds to one of 20 different amino acids used to build a protein. If a mutation disrupts this normal reading frame, then the entire gene sequence following the mutation will be incorrectly read. 

This can result in the addition of the wrong amino acids to the protein and/or the creation of a codon that stops the protein from growing longer.Frameshift Mutation. Imagine that you are reading a great mystery novel. When you get to an important part of the plot, you find that a chapter of the book is missing, either torn from the book or not printed correctly. Because the chapter is missing, none of the following parts of the book make much sense. For DNA, a missing segment can cause the cell to effectively stop reading from that gene. The consequences depend upon the information stored in the part of the genome where the problem occurred. If the gene performs a critical function, a significant medical problem can result.

https://www.genome.gov/genetics-glossary/Frameshift-Mutation#:~:text=%E2%80%8BFrameshift%20Mutation&text=A%20frameshift%20mutation%20in%20a,bases%20when%20making%20a%20protein.

The frameshift mutation is generally considered to be lethal because it could result in radical changes of the chemical composition of the protein sequence behind.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192591/#:~:text=The%20frameshift%20mutation%20is%20generally,of%20the%20protein%20sequence%20behind. 

フレームシフト突然変異は自然界でも時おり発生はするが、こんな人工的な大規模発生はまずあり得ないんですよね。

本来作られるべきポリペプチドよりも、大幅に小さいものが出来上がる。このような場合、真核生物においてはタンパク質は機能しないので、ナンセンス変異依存mRNA分解機構 nonsense mediated mRNA decayによって細胞内で破壊されることになる。

 

ナンセンス変異依存mRNA分解機構（ナンセンスへんいいぞんエムアールエヌエーぶんかいきこう、英：Nonsense-mediated mRNA decay、以下NMD）は、すべての真核生物に存在するmRNAの品質監視機構である。その主要な機能は、何らかの原因（例：インデル）により本来よりDNA上の上流に出現した終止コドンを含むmRNAを分解・除去することにより、最終産物である異常なタンパク質の量を未然に減少させることである^[1]。このような異常なmRNAがタンパク質まで翻訳された場合、最終的に合成されたタンパク質が生命体にとって有害な機能獲得性変異を生じたり、ドミナントネガティブ作用を引き起こしたりする^[2]。

人工的に発生した大規模フレームシフト突然変異にナンセンス変異依存mRNA分解機構で対応可能なのか？

無理じゃまいか？

これは完全にアウトのような…

BBCが必死です。

Covid study: mRNA vaccines could be fine-tuned
6th December 2023, 06:25 HST

The revolutionary messenger ribonucleic acid (mRNA) technology in some Covid vaccines given to millions of people could be fine-tuned for even greater accuracy, UK scientists say.
Genetic instructions in the jab could be tweaked to avoid a harmless tiny "slip" sometimes seen as the body reads the code, the Medical Research Council team suggest.
Existing mRNA vaccines are effective and safe, they say.
Future ones could fight more diseases.

The partly government-funded study, published in the journal Nature, involved detailed lab work on the original Pfizer-BioNTech shot that, three years ago, became the first of its kind to be used to protect people in the pandemic.
By studying mice and then 21 volunteers who had received the vaccine, the researchers discovered about one in three people might experience the slip error.

One of the biggest success stories in medicine, the mRNA shots, which include one made by Moderna, have protected millions of lives, the researchers say. And understanding and updating the science should help mRNA technology tackle more diseases, possibly even cancer, in the future.UK plan for national mRNA cancer vaccine advance

Covid mRNA vaccines work by showing the body's cells a bit of genetic code from the pandemic virus.
This cannot cause infection but can teach the body how to defend itself against Covid-19.
The body reads and translates the code using its own cell machinery, called ribosomes.
The immune system then uses the instructions to make special protective proteins, called antibodies, that can fight Covid.

It is the translation process in the ribosomes that can go slightly wrong, the researchers say.
The end result is still great protection - but there can be a few extra, unintended proteins made too.


Thankfully, these cause no physical issues, the researchers say, based on real-life evidence from the millions of people, including teenagers and children, vaccinated.
Had there been any problems, they would have been spotted early on, they say.
Translating the code is a bit like reading a sentence of three-letter words, such as: "The cat ate the fat rat."

The ribosome occasionally skips forward by a letter or place, called a frameshift, to read: "The cat a tet hef atr."
And the researchers found a simple tweak to some of the code could eradicate these errors, without affecting the desired end product - protection against a dangerous disease.

Slip-resistant coding

Lead researcher Dr James Thaventhiran, from the MRC Toxicology Unit at the University of Cambridge, said: "Research has shown beyond doubt that mRNA vaccination against Covid-19 is safe.
"Billions of doses of the Moderna and Pfizer mRNA vaccines have been safely delivered, saving lives worldwide.
"We need to ensure that mRNA vaccines of the future are as reliable.
"Our demonstration of 'slip-resistant' mRNAs is a vital contribution to future safety of this medicine platform."
Co-researcher Prof Anne Willis said: "This is really important because this technology is amazing and it is going to be revolutionary as a new medicine platform for all sorts of things."

'Easy fix'

Prof Stephen Griffin, an expert in cancer virology, at the University of Leeds, called it a landmark study.
"It matters that we understand that these events are possible - but it by no means implies that the well established population-safety record for these vaccines, which have been administered more than 13 billion times since 2021, should be questioned," he said.
"Moreover, now this has been identified, there is an easy fix."
Future mRNA vaccines should use the slip-resistant coding, the researchers say, as it is scientifically possible some unintended proteins might be capable of triggering an unwanted immune response or side effect.

Any treatment or vaccine can have possible risks or side effects, although not everybody experiences them.

In the UK, about 53 million people received a first dose of Covid vaccine, 50 million a second and more than 40 million a third or booster, according to official data.

Safety continues to be monitored.

The Medicines and Healthcare products Regulatory Agency (MHRA), which does that monitoring in the UK, says the benefits of the vaccines in preventing Covid-19 and serious complications associated with Covid-19 far outweigh any currently known side effects in the majority of patients.

Dr Alison Cave, MHRA chief safety officer, added: "Emerging information is kept under review. We ask anyone who suspects they have experienced a side effect linked with their COVID-19 vaccine to report it via our Yellow Card scheme website."

There have been rare cases of myocarditis - inflammation of the heart muscle - following the mRNA Moderna and the Pfizer vaccines in the UK and it has been listed as a very rare side effect.

The Oxford-AstraZeneca vaccine used early in the pandemic works slightly differently to mRNA vaccines. It has also had some very rare reported side effects, with some people developing dangerous blood clots.
'Promising platform'

Pfizer said: "We welcome independent research and academic discourse to advance the science of mRNA technology.

"The Covid-19 pandemic provided the first opportunity for the use of mRNA platforms.

"To date, hundreds of millions of doses of our Covid-19 vaccines have been administered globally, establishing a positive benefit-risk profile.

"We continue to advance mRNA research and, together with the scientific community, explore new applications for this promising platform to help prevent and treat the spectrum of human disease."

https://www.bbc.com/news/health-67625180

 

もうただひたすらｍRNAワクチン賛美のワケワカメ状態…

、、、（爆ｗｗｗｗｗｗｗｗｗｗｗ