Synthetic mRNA biofunctional RNA tools
Emergence of synthetic mRNA: In vitro synthesis of mRNA and its applications in regenerative medicine
Hyokyoung Kwon, et al.,Biomaterials. Volume 156, February 2018, Pages 172-193
https://www.sciencedirect.com/science/article/abs/pii/S0142961217307639
In this review, we highlight the synthesis and preparation of IVT mRNA and its therapeutic applications. The article includes the design and preparation of IVT mRNA, chemical modification of IVT mRNA, and 3 therapeutic applications and finally, future perspectives and challenges of IVT mRNA are discussed.
Hyokyoung Kwon, et al.,Biomaterials. Volume 156, February 2018, Pages 172-193
https://www.sciencedirect.com/science/article/abs/pii/S0142961217307639
In this review, we highlight the synthesis and preparation of IVT mRNA and its therapeutic applications. The article includes the design and preparation of IVT mRNA, chemical modification of IVT mRNA, and 3 therapeutic applications and finally, future perspectives and challenges of IVT mRNA are discussed.
IVT mRNA in cellular reprogramming
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protein replacement therapy
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mRNA technology isn’t brand-new, and mRNA degrades quickly in the body
before it can have an effect to prevent that, a technique was developed the mRNA is packed into tiny bubbles of fat called lipid nanoparticles shielded inside the lipids the mRNA can reach the cell before then being unloaded. The Pfizer and Moderna vaccines are both messenger RNA vaccines, or mRNA vaccines. RNA stands for ribonucleic acid, a molecule that contains the genetic blueprint for our cells to make proteins. Proteins are used by cells to perform our bodily functions. mRNA vaccines had been studied for decades before COVID-19 emerged. The vaccine technology had been studied in vaccines against other viruses, such as influenza, rabies and Zika, as well as in treatments for cancer. Because of this, we know well how mRNA functions in a vaccine. mRNA vaccines work like an instruction manual. For COVID-19 vaccines, that handbook tells the cell how to create a piece of a “spike protein” that’s unique to SARS-CoV-2 (the virus that causes COVID-19). The vaccine can’t cause COVID-19 infection itself, because it doesn’t carry the actual, live virus — the mRNA encodes only for the spike protein found on the surface of the virus. The spike protein is harmless by itself. Once the body creates that spike protein using the mRNA instructions, the body quickly breaks down those mRNA strands and they dissipate within a few hours or days after injection. The mRNA never enters the nucleus of any cell (where the DNA is located), it doesn’t affect any genetic material in the body, and the mRNA strands are removed from the body through everyday cellular processes. Source How can we know the COVID-19 vaccine won’t have long-term side effects?Author: Nora Colburn, MD, MPH wexnermedical.osu.edu/blog/covid-19-vaccine-long-term-side-effects |
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1027511/Vaccine-surveillance-report-week-42.pdf?fbclid=IwAR11j4naXU6utTu4wzKh-0mTNyPf_6sBoMD4lfBjMmvm36DSbJZ48CHt80o
Summary
Four coronavirus (COVID-19) vaccines have now been approved for use in the UK. Rigorous clinical trials have been undertaken to understand the immune response, safety profile and efficacy of these vaccines as part of the regulatory process. Ongoing monitoring of the vaccines as they are rolled out in the population is important to continually ensure that clinical and public health guidance on the vaccination programme is built upon the best available evidence. UK Health Security Agency, UKHSA, formerly Public Health England (PHE), works closely with the Medicines and Healthcare Regulatory Agency (MHRA), NHS England, and other government, devolved administration and academic partners to monitor the COVID-19 vaccination programme. Details of the vaccine surveillance strategy are set on the page COVID-19: vaccine surveillance strategy (1). As with all vaccines, the safety of COVID-19 vaccines is continuously being monitored by the MHRA. They conclude that overall, the benefits of COVID-19 vaccines outweigh any potential risks (2).
Source:
UK Health Security Agency - GOV.UK (www.gov.uk). Published: 21 October 2021. Publishing reference: GOV-10227
Summary
Four coronavirus (COVID-19) vaccines have now been approved for use in the UK. Rigorous clinical trials have been undertaken to understand the immune response, safety profile and efficacy of these vaccines as part of the regulatory process. Ongoing monitoring of the vaccines as they are rolled out in the population is important to continually ensure that clinical and public health guidance on the vaccination programme is built upon the best available evidence. UK Health Security Agency, UKHSA, formerly Public Health England (PHE), works closely with the Medicines and Healthcare Regulatory Agency (MHRA), NHS England, and other government, devolved administration and academic partners to monitor the COVID-19 vaccination programme. Details of the vaccine surveillance strategy are set on the page COVID-19: vaccine surveillance strategy (1). As with all vaccines, the safety of COVID-19 vaccines is continuously being monitored by the MHRA. They conclude that overall, the benefits of COVID-19 vaccines outweigh any potential risks (2).
Source:
UK Health Security Agency - GOV.UK (www.gov.uk). Published: 21 October 2021. Publishing reference: GOV-10227
Revolution in medicine - BioNTech, mRNA and the Covid-19 vaccine | DW Documentary
14:56
It's expensive and difficult to store and distribute, so it's not necessarily suited to developing countries.
14:56
It's expensive and difficult to store and distribute, so it's not necessarily suited to developing countries.
The benefit of an RNA vaccine is that it works quicker and is perhaps more versatile than a viral vector vaccine nevertheless we still use viral vectors like the one for measles at the Pasteur Institute, the production costs are much lower, the RNA vaccine is an addition to our existing arsenal but we shouldn't believe that all of the other platforms will become obsolete simply because we have an RNA vaccine Revolution in medicine - BioNTech, mRNA and the Covid-19 vaccine | DW Documentary www.youtube.com/watch?v=VMZtG0O9sbU
- 35:33... random errors occur in the virus's genetic code only some of them are relevant though, They alter the properties of the virus thereby creating a mutation for example it can change the virus and make it more easily transmissible and therefore more contagious.
- 36:34 there are viruses for which a vaccine gives you lifelong immunity for example polio or smallpox but this is a virus where we know we have to administer a booster to stay immune
The "M” in mRNA means ‘messenger and RNA stands for ribonucleic acid.
MRNA delivers information for antigen production directly to the cell which produces proteins. Afterwards, these cells present self-produced antigens on their outer shells and trigger a specifically desired immune response. |
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Plants also have RNA viruses
Mechanisms of plant resistance to viruses | Nature Reviews ...https://www.nature.com
R genes confer resistance to organisms including viruses, bacteria, fungi and even nematodes 2. R proteins and their signal-transduction molecules are strikingly similar to the components of the ... Video: Plant Diseases: Viruses www.youtube.com/watch?v=rBn5CUcH7e8 Polio |
- RNA silencing is a highly conserved pathway in animals and plants that functions in development and in the maintenance of genome integrity. Plants have adapted this system for antiviral defence, and plant viruses have in turn developed mechanisms to suppress RNA silencing. Mechanisms of plant resistance to viruses www.nature.com/articles/nrmicro1239
106:56 into video
"Making a virus with pandemic potential and releasing it into the environment...THEY ACTUALLY DID MAKE A POLIO VIRUS AND PUBLISHED IT..."
"Making a virus with pandemic potential and releasing it into the environment...THEY ACTUALLY DID MAKE A POLIO VIRUS AND PUBLISHED IT..."
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It's Alive, But Is It Life: Synthetic Biology and the Future of Creation
https://www.youtube.com/watch?v=rU_pfCtSWF4 For decades, biologists have read and edited DNA, the code of life. Revolutionary developments are giving scientists the power to write it. Instead of tinkering with existing life forms, synthetic biologists may be on the verge of writing the DNA of a living organism from scratch. In the next decade, according to some, we may even see the first synthetic human genome. Join a distinguished group of synthetic biologists, geneticists and bioengineers who are edging closer to breathing life into matter. This program is part of the Big Ideas Series, made possible with support from the John Templeton Foundation. Original Program Date: June 4, 2016 |
Modes of action of Freund's adjuvants in experimental models of autoimmune diseasesA Billiau, P Matthys - Journal of leukocyte biology, 2001 - Wiley Online Library
… various types of studies that provide more insight in the specific alterations of the immune response caused by IFA and … animals with PPD in CFA and then challenging them with PPD‐coated beads, the mRNAs for IFN‐γ and TNF‐α were found to be detectable [89]. From studies … [PDF] researchgate.netOmega-3 fatty acids in inflammation and autoimmune diseasesAP Simopoulos - Journal of the American College of nutrition, 2002 - Taylor & Francis … Omega-3 fatty acids suppress IL-1 mRNA [40,41]. These observations led to studies in patients with inflammatory and autoimmune diseases. The suppression of cytokine synthesis could also be achieved by dietary alteration without fish oil supplementation [34]. The cytokine … [HTML] nih.govMicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseasesR Dai, SA Ahmed - Translational Research, 2011 - Elsevier … The field of miRNA regulation of mammalian genes has tremendous potential. The … The imperfect sequence complementary between miRNA and target mRNA usually leads to the … following phases of studies: (1) to understand the pathogenic contribution of these disease-related … |
[HTML] nature.com[HTML] mRNA vaccines—a new era in vaccinologyN Pardi, MJ Hogan, FW Porter… - Nature reviews Drug …, 2018 - nature.com
… and elucidate the immune pathways activated by various mRNA vaccine platforms, to … (IVT) mRNA in animals was published in 1990, when reporter gene mRNAs were injected into … two clinical trials of mRNA vaccines for infectious diseases were somewhat modest, leading to … Save Cite Cited by 1362 Related articles All 13 versions [PDF] jimmunol.orgFree from PublisherIL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10-and IL-4-deficient and transgenic miceE Bettelli, MP Das, ED Howard… - The Journal of …, 1998 - Am Assoc Immnol … studies, examination of brains and spinal cords from diseased animals revealed the presence of mRNA for IFN-γ and TNF-α during clinical episodes, whereas mRNA … Cytokines play a pivotal role in the initiation or regulation of autoimmune disease, and detailed in vivo studies … [HTML] nature.com[HTML] mRNA-based therapeutics—developing a new class of drugsU Sahin, K Karikó, Ö Türeci - Nature reviews Drug discovery, 2014 - nature.com … Early clinical trials with protamine-complexed IVT mRNA as well as mRNA combined with GM-CSF revealed that intradermal vaccination with these compounds is feasible, safe and can lead to the induction of antigen-specific antibody and T cell immune responses 17,92 . This … |
Researcher: ‘We Made a Big Mistake’ on COVID-19 Vaccine
rightsfreedoms.wordpress.com/2021/06/16/researcher-we-made-a-big-mistake-on-covid-19-vaccine/
“It’s the first time ever scientists have been privy to seeing where these messenger RNA [mRNA] vaccines go after vaccination,” Bridle told Pierson.
“Is it a safe assumption that it stays in the shoulder muscle? The short answer is: absolutely not. It’s very disconcerting … We have known for a long time that the spike protein is a pathogenic protein. It is a toxin. It can cause damage in our body if it gets into circulation … The spike protein on its own is almost entirely responsible for the damage to the cardiovascular system, if it gets into circulation.”
The mRNA enters your bloodstream and accumulates in a variety of organs, primarily your spleen, bone marrow, liver, adrenal glands and, in women, the ovaries. The spike protein also travel to your heart, brain and lungs, where bleeding and or blood clots can occur as a result, and is expelled in breast milk.
“It’s the first time ever scientists have been privy to seeing where these messenger RNA [mRNA] vaccines go after vaccination,” Bridle told Pierson.
“Is it a safe assumption that it stays in the shoulder muscle? The short answer is: absolutely not. It’s very disconcerting … We have known for a long time that the spike protein is a pathogenic protein. It is a toxin. It can cause damage in our body if it gets into circulation … The spike protein on its own is almost entirely responsible for the damage to the cardiovascular system, if it gets into circulation.”
The mRNA enters your bloodstream and accumulates in a variety of organs, primarily your spleen, bone marrow, liver, adrenal glands and, in women, the ovaries. The spike protein also travel to your heart, brain and lungs, where bleeding and or blood clots can occur as a result, and is expelled in breast milk.
mRNA technology isn’t brand-new, and mRNA degrades quickly in the body
before it can have an effect to prevent that, a technique was developed the mRNA is packed into tiny bubbles of fat called lipid nanoparticles shielded inside the lipids the mRNA can reach the cell before then being unloaded.
The Pfizer and Moderna vaccines are both messenger RNA vaccines, or mRNA vaccines. RNA stands for ribonucleic acid, a molecule that contains the genetic blueprint for our cells to make proteins. Proteins are used by cells to perform our bodily functions.
mRNA vaccines had been studied for decades before COVID-19 emerged. The vaccine technology had been studied in vaccines against other viruses, such as influenza, rabies and Zika, as well as in treatments for cancer.
Because of this, we know well how mRNA functions in a vaccine.
mRNA vaccines work like an instruction manual. For COVID-19 vaccines, that handbook tells the cell how to create a piece of a “spike protein” that’s unique to SARS-CoV-2 (the virus that causes COVID-19).
The vaccine can’t cause COVID-19 infection itself, because it doesn’t carry the actual, live virus — the mRNA encodes only for the spike protein found on the surface of the virus. The spike protein is harmless by itself.
Once the body creates that spike protein using the mRNA instructions, the body quickly breaks down those mRNA strands and they dissipate within a few hours or days after injection. The mRNA never enters the nucleus of any cell (where the DNA is located), it doesn’t affect any genetic material in the body, and the mRNA strands are removed from the body through everyday cellular processes.
Source
How can we know the COVID-19 vaccine won’t have long-term side effects?Author: Nora Colburn, MD, MPH
wexnermedical.osu.edu/blog/covid-19-vaccine-long-term-side-effects
before it can have an effect to prevent that, a technique was developed the mRNA is packed into tiny bubbles of fat called lipid nanoparticles shielded inside the lipids the mRNA can reach the cell before then being unloaded.
The Pfizer and Moderna vaccines are both messenger RNA vaccines, or mRNA vaccines. RNA stands for ribonucleic acid, a molecule that contains the genetic blueprint for our cells to make proteins. Proteins are used by cells to perform our bodily functions.
mRNA vaccines had been studied for decades before COVID-19 emerged. The vaccine technology had been studied in vaccines against other viruses, such as influenza, rabies and Zika, as well as in treatments for cancer.
Because of this, we know well how mRNA functions in a vaccine.
mRNA vaccines work like an instruction manual. For COVID-19 vaccines, that handbook tells the cell how to create a piece of a “spike protein” that’s unique to SARS-CoV-2 (the virus that causes COVID-19).
The vaccine can’t cause COVID-19 infection itself, because it doesn’t carry the actual, live virus — the mRNA encodes only for the spike protein found on the surface of the virus. The spike protein is harmless by itself.
Once the body creates that spike protein using the mRNA instructions, the body quickly breaks down those mRNA strands and they dissipate within a few hours or days after injection. The mRNA never enters the nucleus of any cell (where the DNA is located), it doesn’t affect any genetic material in the body, and the mRNA strands are removed from the body through everyday cellular processes.
Source
How can we know the COVID-19 vaccine won’t have long-term side effects?Author: Nora Colburn, MD, MPH
wexnermedical.osu.edu/blog/covid-19-vaccine-long-term-side-effects
Why do some people have side effects with COVID-19 vaccines while others do not?
Scientists do not fully understand why this is the case, but the differences could be due to a combination of a person’s age, genetics and past exposure to other viruses, including common-cold coronaviruses.
Healthy young adults, adolescents and children who contracted the virus have been the least likely to develop severe complications from COVID-19, including death. In fact, 100% of the COVID-involved deaths of Canadians under the age of 45 as of July 31 2001 had at least one other disease or condition certified on the medical certificate of death. The proportion of those with at least one other disease or condition decreases with age, ranging from 93% for those aged 45 to 64 to 89% for those aged 85 years or older. Source: 1. https://www150.statcan.gc.ca/.../article/00087-eng.htm. 2. COVID-19 death comorbidities in Canada (statcan.gc.ca) Nevertheless, VAERS Table of Reportable Events Following Vaccination indicates death among children can and do occur. Source: vaers.hhs.gov/docs/VAERS_Table_of_Reportable_Events_Following_Vaccination.pdf Note:: A BAN was placed on all Social Media regarding the Vaccine thus arousing more suspicion and blocking transparency In October 2021.
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Which disease is caused by RNA virus? Human diseases causing RNA viruses include:
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How does RNA cause disease?
In eukaryotes, RNA is transcribed from genomic DNA. RNA molecules undergo multiple post-transcriptional processes such as splicing, editing, modification, translation, and degradation. A defect, mis-regulation, or malfunction of these processes often results in diseases in humans, referred to as 'RNA diseases'. What kills RNA virus? Once the virus is inside human cells, a protein called ZAP can identify viral RNAs by binding to a precise motif, a combination of two nucleotides called CpG. This allows the cell to destroy the viral RNA, thus preventing the virus from multiplying. |
Image: True Health - Pharmaceutical Control Of Your Lives https://www.youtube.com/watch?v=r_Wqd897YCQ 36:46 Pfizer vaccine antibodies may disappear in seven months study shows. Now you can't say that on the news because you can't question anything, in fact that that would qualify Medscape as a domestic terrorist. |
https://namelyliberty.com/dr-robert-malone-inventor-of-mrna-vaccines-talks-about-dangers-of-covid-19-mrna-vaccines/
Dangers of COVID-19 mRNA Vaccines Topics covered include antibody dependent enhancement and vaccines for pregnant women. |
Meeting of the COVID-19 Giants Geert Vanden Bossche and Robert Malone MD www.youtube.com/watch?v=qP31cfD3YOY ALT: https://www.bitchute.com/video/TjrK3mlRC98D/ |
RNA Viral families
Orthomyxoviridae:
Influenza Paramyoxviridae: Mumps, measles, respiratory infections Rhabdoviridae: rabies Togaviridae: yellow fever, rubella, encephalitis |
Retroviridae:
AIDS, T-cell leukemia Reoviridae: Rotavirus, diarrheal disease, encephalitis Picornaviridae: polio, hepatitis A Coronaviridae: Respiratory infection |
Caliciviridae:
Norwalk virus gasteroenteritis Filoviridae: Ebola virus hemorrhagic fever Arenaviridae: Lassa virus hemorrhagic fever Bunyaviridae: Encephalitis |
Retroviridae
Simple: Alpharetrovirus, Gammaretrovirus
Alpharetrovirus Retrovirus group that has all 4 proteins, and has Rous Sarcoma virus Gammaretrovirus Retrovirus that has the largest number of members and has Feline Leukemia virus Complex: Deltaretrovirus, Epsilonretrovirus, Lentiviruses Deltaretrovirus Bovine leukemia virus is in this group of retroviruses: Epsilonvirus Retrovirus that has Walleye Dermal Sarcoma virus and is only endogenous found in fish and reptiles Lentivirus This group from Retroviridae is a slow virus meaning it has a long incubation period and includes HIV and FIV |
Today, lentiviral vectors are major tools for basic and translational research, enabling scientists to :
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Lentivirus
This group from Retroviridae is a slow virus meaning it has a long incubation period and includes:
Transmission route/pathogenesis of FIV: Feline Immunodeficiency Virus
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Avian and Human strains of Swine influenza virus
Swine influenza virus
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West Nile Virus
A virus part of the genera Flavivirus that causes febrile disease in humans
Retroviruses
Alpharetrovirus
Retrovirus group that has all 4 proteins, and has Rous Sarcoma virus Gammaretrovirus Retrovirus that has the largest number of members and has Feline Leukemia virus Deltaretrovirus Bovine leukemia virus is in this group of retroviruses: Epsilonvirus Retrovirus that has Walleye Dermal Sarcoma virus and is only endogenous found in fish and reptiles Lentivirus This group from Retroviridae is a slow virus meaning it has a long incubation period and includes HIV and FIV Wasting syndrome and atrophy of the thymus (leads to recurrent infections) Feline Leukemia virus has a low prevalence, higher in multi-cat households, is more likely in young cats with poor hygienic conditions. Aged cats are resistant. |
Flaviviridae
An enveloped viral family that caused yellow fever transmitted by mosquitoes with 4 important genera (pestivirus, flavivirus, hepacivirus, and pegivirus)
Prions
Scrapie This prion disease is in sheep and has a very long (2-5 year) incubation period and is clinically show as fine tremors, ataxia, and intense pruritus. It does this by neuronal vacuolation and degeneration Bovine spongiform encephalopathy (mad cow disease) This prion disease is transmitted through meat+bone meal derived from ruminant meat or offal and is shown with hyperesthesia with kicking during milking, progressive apprehensive behavior, and hind limb ataxia. Causes issues by neuronal vacuolation and lesions in the midbrain, brainstem and cervical spinal cord |
Coronaviridae
Coronaviridae is a family of enveloped, positive-strand RNA viruses which infect amphibians, birds, and mammals. The group includes the subfamilies Letovirinae and Orthocoronavirinae; the members of the latter are known as coronaviruses. The viral genome is 26–32 kilobases in length.Wikipedia
Coronaviridae is a family of enveloped, positive-strand RNA viruses which infect amphibians, birds, and mammals. The group includes the subfamilies Letovirinae and Orthocoronavirinae; the members of the latter are known as coronaviruses. The viral genome is 26–32 kilobases in length.Wikipedia
Characteristics of corona viruses :
shape: spherical envelope: has and envelope, ssRNA+ size: largest known viral RNA genome genome type/shape/charge/size: coiled helical nucleocapsid Number of genes are in the genome: 6-10= 20 proteins Children don't get sick from corona virus because they have different immune systems that can rapidly produce antibodies, ACE-2 may be different in children |
Discovery of the coronaviruses:
47D11 neutralizes the spike protein by binding to the conserved part of the spike protein that is the same in SARS-CoV-1 and 2 which is why it can neutralize both SARS-CoV-1 and 2. |