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A one-in-three-trillion chance through natural evolution!

So it obviously NATURAL

Blackjack
Blackjack Male
10 months ago
A group of researchers discovered that COVID-19 (SARS-CoV-2) has a small piece of DNA that matched the genetic sequence patented by Moderna Inc. three years before the start of the pandemic in 2021.

A Basic Local Alignment Search Tool (BLAST) search for the 12-nucleotide insertion led us to a 100% reverse match in a proprietary sequence (SEQ ID11652, nt 2751-2733) found in the U.S. patent 9,587,003 filed on February 4, 2016. In bioinformatics, BLAST is an algorithm and program for comparing primary biological sequence information, such as the amino-acid sequences of proteins or the nucleotides of DNA and/or RNA sequences.

Moderna filed the patent as part of its cancer research division. COVID-19 is made up of 30,000 letters of genetic code that carry the information it needs to spread that are known as nucleotides. The commonality was a very small piece made up of 19 nucleotides. Analysis of the original COVID-19 genome found the virus shares a sequence of 19 specific letters with a genetic section owned by Moderna, which has a total of 3,300 nucleotides, according to the report.

The findings were published in Frontiers in Virology and the team includes Akhil Varshney from Dr Shroff Charity Eye Hospital in New Delhi. The study is titled, “MSH3 Homology and Potential Recombination Link to SARS-CoV-2 Furin Cleavage Site.”

“The matching code may have originally been introduced to the COVID-19 genome through infected human cells expressing the MSH3 gene,” wrote Dr Balamurali Ambati, from the University of Oregon, in the study.

Moderna CEO Bancel Responds
The researchers suggest the virus may have mutated to have a furin cleavage site during experiments on human cells in a lab. However, the team claimed that there is a one-in-three-trillion chance Moderna’s sequence randomly appeared through natural evolution. This research fuels the “lab leak theory” of COVID-19. If there was any link of Moderna to a possible lab leak, would hit the company with major lawsuits. Moderna, along with Pfizer Inc., generated mounds of revenue selling mRNA COVID-vaccines to governments around the world.



I REPEAT - A ONE-IN-THREE TRILLION CHANCE MODERNA'S SEQUENCE NATURALL APPEARED THROUGH NATURAL SELECTION



Moderna CEO Stephane Bancel appeared on FOX Business’ Maria Bartiromo show on February 24, 2022.

Bartiromo said that “scientists have found a tiny chunk of DNA that matches sequences patened by Moderna three years before the pandemic began.”

Bancel responded, “My scientists are looking into those data to see how accurate they are or not. As I have said before the hypothesis of an escape from a lab by accident is possible… Human makes mistakes.”

When the COVID-19 pandemic started, social media sites like Twitter and YouTube (owned by Alphabet) labeled the lab leak theory as misinformation and censored accounts. Now the Lab Leak theory has come up as a broad possible theory of how COVID-19 came to pass. The lab leak theory argues COVID-19 escaped from the Wuhan Institute of Virology. The initial theory that was of the origins of COVID–19 at the time pushed by all major media and the World Health Organization was that the virus occurred in bats and jumped to humans (possibly at a wet market in Wuhan).

Moderna
mRNA medicines are a relatively new scientific field and, as the field continues to mature, patent applications are being processed by national patent offices around the world. Moderna had revenue of US$ 60 million in 2019, US$ 803 million in 2020, and US$ 18.471 billion in 2021.
tsunamiwarrior
tsunamiwarrior Male
10 months ago
RNA therapeutics are a new class of medications based on ribonucleic acid (RNA). Research has been working on clinical use since the 1990s, with significant success in cancer therapy in the early 2010s.[1] In 2020 and 2021, mRNA vaccines have been developed globally for use in combating the coronavirus disease (COVID-19 pandemic).[2] The Pfizer–BioNTech COVID-19 vaccine was the first mRNA vaccine approved by a medicines regulator, followed by the Moderna COVID-19 vaccine, and others.

The main types of RNA therapeutics are those based on messenger RNA (mRNA), antisense RNA (asRNA), RNA interference (RNAi), and RNA aptamers. Of the four types, mRNA-based therapy is the only type which is based on triggering synthesis of proteins within cells, making it particularly useful in vaccine development.[3] Antisense RNA is complementary to coding mRNA and is used to trigger mRNA inactivation to prevent the mRNA from being used in protein translation.[4] RNAi-based systems use a similar mechanism, and involve the use of both small interfering RNA (siRNA) and micro RNA (miRNA) to prevent mRNA translation.[5][6] However, RNA aptamers are short, single stranded RNA molecules produced by directed evolution to bind to a variety of biomolecular targets with high affinity thereby affecting their normal in vivo activity.[7][8][9]

RNA is synthesized from template DNA by RNA polymerase with messenger RNA (mRNA) serving as the intermediary biomolecule between DNA expression and protein translation. Because of its unique properties (such as its typically single-stranded nature and its 2' OH group) as well as its ability to adopt many different secondary/tertiary structures, both coding and noncoding RNAs have attracted special attention in medicine. Research has begun to explore RNAs potential to be used for therapeutic benefit, and unique challenges have occurred during drug discovery and implementation of RNA therapeutics.
tsunamiwarrior
tsunamiwarrior Male
10 months ago
mRNA
Messenger RNA (mRNA) is a single-stranded RNA molecule that is complementary to one of the DNA strands of a gene.[11] An mRNA molecule transfers a portion of the DNA code to other parts of the cell for making proteins.[12] DNA therapeutics needs access to the nucleus to be transcribed into RNA, and its functionality depends on nuclear envelope breakdown during cell division. However, mRNA therapeutics do not need to enter into the nucleus to be functional since it will be translated immediately once it has reached to the cytoplasm.[13] Moreover, unlike plasmids and viral vectors, mRNAs do not integrate into the genome and therefore do not have the risk of insertional mutagenesis,[14] making them suitable for use in cancer vaccines, tumor immunotherapy and infectious disease prevention.[15]

Discovery and development
In 1953, Alfred Day Hershey reported that soon after infection with phage, bacteria produced a form of RNA at a high level and this RNA was also broken down rapidly.[16] However, the first clear indication of mRNA was from the work of Elliot Volkin and Lazarus Astrachan in 1956 by infecting E.Coli with T2 bacteriophages and putting them into the medium with 32P.[17][18] They found out that the protein synthesis of E.Coli was stopped and phage proteins were synthesized.[19] Then, in May 1961, their collaborated researchers Sydney Brenner, François Jacob, and Jim Watson announced the isolation of mRNA.[20][21] For a few decades after mRNA discovery, people focused on understanding the structural, functional, and metabolism pathway aspects of mRNAs. However, in 1990, Jon A. Wolff demonstrated the idea of nucleic acid-encoded drugs by direct injecting in vitro transcribed (IVT) mRNA or plasmid DNA (pDNA) into the skeletal muscle of mice which expressed the encoded protein in the injected muscle.[22][23][24]

Once IVT mRNA has reached the cytoplasm, the mRNA is translated instantly. Thus, it does not need to enter the nucleus to be functional.[25] Also, it does not integrate into the genome and therefore does not have the risk of insertional mutagenesis.[26] Moreover, IVT mRNA is only transiently active and is completely degraded via physiological metabolic pathways.[27] Due to these reasons, IVT mRNA has undergone extensive preclinical investigation.
tsunamiwarrior
tsunamiwarrior Male
10 months ago
Mechanisms
In vitro transcription(IVT) is performed on a linearized DNA plasmid template containing the targeted coding sequence. Then, naked mRNA or mRNA complexed in a nanoparticle will be delivered systemically or locally. After then, a part of the exogenous naked mRNA or complexed mRNA is going through cell-specific mechanisms. Once in the cytoplasm, the IVT mRNA is translated by the protein synthesis machinery.[28][29]

There are two identified RNA sensors, toll-like receptors (TLRs) and the RIG-I-like receptor family. TLRs are localized in the endosomal compartment of cells, such as DCs and macrophages.[30] RIG-I-like family is as a pattern recognition receptor (PRR).[31] However, the immune response mechanisms and process of mRNA vaccine recognition by cellular sensors and the mechanism of sensor activation are still unclear.[29]
tsunamiwarrior
tsunamiwarrior Male
10 months ago
Cancer immunotherapy
In 1995, Robert Conry demonstrated that intramuscular injection of naked RNA encoding carcinoembryonic antigen elicited antigen-specific antibody responses.[32] Then, it was elaborated by demonstrating that dendritic cells(DCs) exposed to mRNA coding for specific antigens or to total mRNA extracted from tumor cells and injected into tumor-bearing mice induced T cell immune responses and inhibited the growth of tumors.[33] Then, researchers started to approach mRNA transfected DCs using vaccines based on ex vivo IVT mRNA-transfected DCs.[34] Meanwhile, Argos Therapeutics had initiated a Phase III clinical trial using DCs with advanced renal cell carcinoma in 2015 (NCT01582672) but it was terminated due to the lack of efficacy.[35]

For further application, IVT mRNA was optimized for in situ transfections of DCs in vivo. It improved the translation efficiency and stability of IVT mRNA and enhanced the presentation of the mRNA-encoded antigen on MHC class I and II molecules.[36][37] Then, they found out that the direct injection of naked IVT mRNA into lymph nodes was the most effective way to induce T cell responses.[38] Based on this discovery, first-in-human testing of the injection of naked IVT mRNA encoding cancer antigens by BioNTech has started with patients with melanoma (NCT01684241).[39]

Recently, the new cancer immunotherapy, the combining of self-delivering RNA(sd-rxRNA) and adoptive cell transfer(ACT) therapy, was invented by RXi Pharmaceuticals and the Karolinska Institute. In this therapy, the sd-rxRNA eliminated the expression of immunosuppressive receptors and proteins in therapeutic immune cells so it improved the ability of immune cells to destroy the tumor cells. Then, the PD-1 targeted sd-rxRNA helped increasing the anti-tumor activity of tumor-infiltrating lymphocytes (TIL) against melanoma cells.[40][41] Based on this idea, the mRNA-4157 has been tested and passed phase I clinical trial.[42]

Cytosolic nucleic acid-sensing pathways can enhance immune response to cancer. RIG-I agonist, stem loop RNA (SLR) 14. Tumor growth was significantly delayed and extended survival in mice. SLR14 improved antitumor efficacy of anti-PD1 antibody over single-agent treatment. SLR14 was absorbed by CD11b+ myeloid cells in the tumor microenvironment. Genes associated with immune defense were significantly up-regulated, along with increased CD8+ T lymphocytes, NK cells, and CD11b+ cells. SLR14 inhibited nonimmunogenic B16 tumor growth, leaving immune memory.[43]
Blackjack
Blackjack Male
10 months ago
Good to see that I lead and you as usual follow like the good little reliable second rate person you have become.

Some have to set the direction for the lost and disorientated, and thank you for your contribution again which like you no one can or will understand or read.

Lets be honest you are flattering me - and securing my position as an innovator
tsunamiwarrior
tsunamiwarrior Male
10 months ago
Vaccines
Main article: RNA vaccine
In 1993, the first success of an mRNA vaccine was reported in mice, by using liposome-encapsulated IVT mRNA which is encoding the nucleoprotein of influenza that induced virus-specific T cells.[44] Then, IVT mRNA was formulated with synthetic lipid nanoparticles and it induced protective antibody responses against the respiratory syncytial virus(RSV) and influenza virus in mice.[45]

There are a few different types of IVT mRNA-based vaccine development for infectious diseases. One of the successful types is using self-amplifying IVT mRNA that has sequences of positive-stranded RNA viruses. It was originally developed for a flavivirus and it was workable with intradermal injection. One of the other ways is injecting a two-component vaccine which is containing an mRNA adjuvant and naked IVT mRNA encoding influenza hemagglutinin antigen only or in combination with neuraminidase encoding IVT mRNA.[46]

For example, for the HIV treatment, vaccines are using DCs transfected with IVT mRNA that is encoding HIV proteins. There are a few phase I and II clinical trials using IVT mRNA encoding combinations and it shows that antigen-specific CD8+ and CD4+ T cell responses can be induced. However, no antiviral effects have been observed in the clinical trial.[47][48]

One of the other mRNA vaccines is for COVID-19. The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) outbreaks in December 2019 and spread all over the world, causing a pandemic of respiratory illness designated coronavirus disease 2019 (Covid-19).[49] The Moderna COVID-19 vaccine, manufactured by Moderna since 2020, is a lipid nanoparticle (LNP) encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike(S)-2P antigen of SARS-CoV-2 with a transmembrane anchor.[50][51]
tsunamiwarrior
tsunamiwarrior Male
10 months ago
Anti-viral
In 2021, SLR14 was reported to prevent infection in the lower respiratory tract and severe disease in an interferon type I (IFN-I)–dependent manner in mice. Immunodeficient mice with chronic SARS-CoV-2 infection experienced near-sterilizing innate immunity with no help from the adaptive immune system.[52]

Limitations
There are many challenges for the successful translation of mRNA into drugs because mRNA is a very large and heavy molecule(10^5 ~ 10^6 Da). Moreover, mRNA is unstable and easily degraded by nucleases, and it also activates the immune systems.[53] Furthermore, mRNA has a high negative charge density and it reduces the permeation of mRNA across cellular membranes.[54] Due to these reasons, without the appropriate delivery system, mRNA is degraded easily and the half-life of mRNA without a delivery system is only around 7 hours.[55] Even though some degrees of challenges could be overcome by chemical modifications, delivery of mRNA remains an obstacle. The methods that have been researched to improve the delivery system of mRNA are using microinjection, RNA patches (mRNA loaded in a dissolving micro-needle), gene gun, protamine condensation, RNA adjuvants, and encapsulating mRNA in nanoparticles with lipids.[53][56][57]

Even though In Vitro Translated (IVT) mRNA with delivery agents showed improved resistance against degradation, it needs more studies on how to improve the efficiency of the delivery of naked mRNA in vivo.[23]
Blackjack
Blackjack Male
10 months ago
Come on cut and paste more show me what you are made of copy the lot and repeat it - we both know you do not have clue what its about - but please try harder you are slipping - as I said some set the pace and the less evolved follow - I want another 12 PAGES - it does not matter what you write as you are an idiot trying to be KLeva - and I like to inspire my followers and you are so very dedicated
NeverSayNever
NeverSayNever Female
10 months ago
Kudos Jack.
Greencare
Greencare Female
10 months ago
COUGH
Blackjack
Blackjack Male
10 months ago
Common lad you are starting to let your ignorant side down I asked for a dozen - BUCK UP!! Please do as you are told and respond


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