#RNA interference

[science-sculpt]

Exploring RNA Interference

Imagine a molecular switch within your cells, one that can selectively turn off the production of specific proteins. This isn't science fiction; it's the power of RNA interference (RNAi), a groundbreaking biological process that has revolutionized our understanding of gene expression and holds immense potential for medicine and beyond.

The discovery of RNAi, like many scientific breakthroughs, was serendipitous. In the 1990s, Andrew Fire and Craig Mello were studying gene expression in the humble roundworm, Caenorhabditis elegans (a tiny worm). While injecting worms with DNA to study a specific gene, they observed an unexpected silencing effect - not just in the injected cells, but throughout the organism. This puzzling phenomenon, initially named "co-suppression," was later recognized as a universal mechanism: RNAi.

Their groundbreaking work, awarded the Nobel Prize in 2006, sparked a scientific revolution. Researchers delved deeper, unveiling the intricate choreography of RNAi. Double-stranded RNA molecules, the key players, bind to a protein complex called RISC (RNA-induced silencing complex). RISC, equipped with an "Argonaut" enzyme, acts as a molecular matchmaker, pairing the incoming RNA with its target messenger RNA (mRNA) - the blueprint for protein production. This recognition triggers the cleavage of the target mRNA, effectively silencing the corresponding gene.

So, how exactly does RNAi silence genes? Imagine a bustling factory where DNA blueprints are used to build protein machines. RNAi acts like a tiny conductor, wielding double-stranded RNA molecules as batons. These batons bind to specific messenger RNA (mRNA) molecules, the blueprints for proteins. Now comes the clever part: with the mRNA "marked," special molecular machines chop it up, effectively preventing protein production. This targeted silencing allows scientists to turn down the volume of specific genes, observing the resulting effects and understanding their roles in health and disease.

The intricate dance of RNAi involves several key players:dsRNA: The conductor, a long molecule with two complementary strands. Dicer: The technician, an enzyme that chops dsRNA into small interfering RNAs (siRNAs), about 20-25 nucleotides long. RNA-induced silencing complex (RISC): The ensemble, containing Argonaute proteins and the siRNA. Target mRNA: The specific "instrument" to be silenced, carrying the genetic instructions for protein synthesis.

The siRNA within RISC identifies and binds to the complementary sequence on the target mRNA. This binding triggers either:Direct cleavage: Argonaute acts like a molecular scissors, severing the mRNA, preventing protein production. Translation inhibition: RISC recruits other proteins that block ribosomes from translating the mRNA into a protein.

From Labs to Life: The Diverse Applications of RNAi

The ability to silence genes with high specificity unlocks various applications across different fields:

Unlocking Gene Function: Researchers use RNAi to study gene function in various organisms, from model systems like fruit flies to complex human cells. Silencing specific genes reveals their roles in development, disease, and other biological processes.

Therapeutic Potential: RNAi holds immense promise for treating various diseases. siRNA-based drugs are being developed to target genes involved in cancer, viral infections, neurodegenerative diseases, and more. Several clinical trials are underway, showcasing the potential for personalized medicine.

Crop Improvement: In agriculture, RNAi offers sustainable solutions for pest control and crop development. Silencing genes in insects can create pest-resistant crops, while altering plant genes can improve yield, nutritional value, and stress tolerance.

Beyond the Obvious: RNAi applications extend beyond these core areas. It's being explored for gene therapy, stem cell research, and functional genomics, pushing the boundaries of scientific exploration.

Despite its exciting potential, RNAi raises ethical concerns. Off-target effects, unintended silencing of non-target genes, and potential environmental risks need careful consideration. Open and responsible research, coupled with public discourse, is crucial to ensure we harness this powerful tool for good.

RNAi, a testament to biological elegance, has revolutionized our understanding of gene regulation and holds immense potential for transforming various fields. As advancements continue, the future of RNAi seems bright, promising to silence not just genes, but also diseases, food insecurity, and limitations in scientific exploration. The symphony of life, once thought unchangeable, now echoes with the possibility of fine-tuning its notes, thanks to the power of RNA interference.

[gpstudios]

Celebrating World RNA Day: Exploring the Wonders of Ribonucleic Acid 🌍🔬

Happy World RNA Day! 🌍🔬 Celebrate the incredible world of RNA and its vital role in biology and medicine. Learn about RNA, support research, and promote STEM education. #WorldRNADay #RNAResearch

Introduction Happy World RNA Day! 🌍🔬 Celebrated annually on August 1st, World RNA Day is dedicated to recognizing and appreciating the crucial role of RNA (ribonucleic acid) in biology and medicine. RNA is essential for numerous biological processes, including protein synthesis and gene regulation. Today, we celebrate the scientific discoveries and innovations surrounding RNA and its profound…

[medicomunicare]

Galectina-1: non solo marker ma anche potenziale bersaglio per contrastare il cancro al fegato

Il carcinoma epatico (HCC) o cancro al fegato, è uno dei tumori più comuni al mondo. E i numeri sono in aumento, con tassi di incidenti più che triplicati rispetto agli anni ’80. La malattia può essere anche piuttosto mortale: negli stadi avanzati il tasso di sopravvivenza a cinque anni è inferiore al 20%. I ricercatori del Davis Comprehensive Cancer Center dell’Università della California hanno…

[vivianascarincilibellulalab]

Ecofemminismo della petunia

Del giardino mi piace soprattutto quanto sia vicino all’imponderabile, a quel punto ineffabile in cui natura e cultura, fisica e metafisica, tangibile e simbolico coabitano in un tempo che è dentro e fuori le cose. Un tempo pieno di sorprese. Non ponderabile significa non misurabile ma non per questo inesistente. In passato quando il colore, la luce, il calore, l’elettricità, il magnetismo non…

[soumyafwr]

RNA Interference (RNAi) Drug Delivery Market Share, Overview, Competitive Analysis and Forecast 2031

[literaryvein-reblogs]

Hello! First of all, thank you for the wonderful content! It's a real joy, and an enrichment, food for both the brain and the heart! I was wondering if through your treasures, you could find some writing notes/words/concepts/vocabulary relating to genetic engineering? Like...creating a virus, and a vaccine for it, modifying the virus so it has certain specific effects.... Thank you in advance!

Writing Notes: Virus & Vaccine

References How Viruses Work; Replication Cycle; Mutation, Variants, Strains, Genetically Engineering Viruses; Writing Tips; Creating your Fictional Virus & Vaccine

Virus - an infectious microbe consisting of a segment of nucleic acid (either DNA or RNA) surrounded by a protein coat.

It is a tiny lifeform that is a collection of genes inside a protective shell. Viruses can invade body cells where they multiply, causing illnesses.

It cannot replicate alone; instead, it must infect cells and use components of the host cell to make copies of itself. Often, a virus ends up killing the host cell in the process, causing damage to the host organism.

Well-known examples of viruses causing human disease include AIDS, COVID-19, measles and smallpox. Examples of viruses:

Viruses are even smaller than bacteria and can invade living cells—including bacteria. They may interfere with the host genes, and when they move from host to host, they may take host genes with them.

Bacteriophages (also known as phages)—viruses that infect and kill bacteria.

Size differential between virus and bacterium

Viruses are measured in nanometers (nm).

They lack the cellular structure of bacteria, being just particles of protein and genetic material.

How Viruses Work

Viruses use an organism’s cells to survive and reproduce.

They travel from one organism to another.

Viruses can make themselves into a particle called a virion.

This allows the virus to survive temporarily outside of a host organism. When it enters the host, it attaches to a cell. A virus then takes over the cell’s reproductive mechanisms for its own use and creates more virions.

The virions destroy the cell as they burst out of it to infect more cells.

Viral shedding - when an infected person releases the virus into the environment by coughing, speaking, touching a surface, or shedding skin.

Viruses also can be shed through blood, feces, or bodily fluids.

Virus Replication Cycle

While the replication cycle of viruses can vary from virus to virus, there is a general pattern that can be described, consisting of 5 steps:

Attachment – the virion attaches to the correct host cell.

Penetration or Viral Entry – the virus or viral nucleic acid gains entrance into the cell.

Synthesis – the viral proteins and nucleic acid copies are manufactured by the cells’ machinery.

Assembly – viruses are produced from the viral components.

Release – newly formed virions are released from the cell.

Mutations, Variants, and Strains

Not all mutations cause variants and strains. Below are definitions that explain how mutations, variants, and strains differ.

Mutation - errors in the replication of the virus’s genetic code; can be beneficial to the virus, deleterious to the virus, or neutral

Variants - viruses with these mutations are called variants; the Delta and Omicron variants are examples of coronavirus mutations that cause different symptoms from the original infection

Strains - variants that have different physical properties are called strains; these strains may have different behaviors or mechanisms for infection or reproduction

Genetically Engineering Viruses

Using reverse genetics, the sequence of a viral genome can be identified, including that of its different strains and variants.

This enables scientists to identify sequences of the virus that enable it to bind to a receptor, as well as those regions that cause it to be so virulent.

Vaccine - a special preparation of substances that stimulate an immune response, used for inoculation

Vaccines & Fighting Viruses with Viruses

Common pathogenic viruses can be genetically modified to make them less pathogenic, such that their virulent properties are diminished but can still be recognized by the immune system to produce a robust immune response against. They are described as live attenuated.

This is the basis of many successful vaccines and is a better alternative than traditional vaccine development which typically includes heat-mediated disabling of viruses that tend to be poorer in terms of immunogenicity.

Viruses can also be genetically modified to ‘fight viruses’ by boosting immune cells to make more effective antibodies, especially where vaccines fail. Where vaccines fail, it is often due to the impaired antibody production by B-cells, even though antibodies can be raised against such viruses – including HIV, EBV, RSV & cold-viruses.

Related Articles: Modified virus used to kill cancer cells ⚜ Genetic Engineering ⚜ Engineering Bacterial Viruses ⚜ Benefits of Viruses

A Few Writing Tips

As more writers look to incorporate infectious diseases into their work, there are quite a few things writers should keep in mind:

Don’t anthropomorphize. Really easy to do, but scientifically wrong. Viruses don’t want to kill you; bacteria don’t want to infect you; parasites don’t want to make your blood curdle. None of these things are big enough to be sentient to want to do anything. They just do it (or don’t do it).

Personal protective equipment. This includes wearing gloves, lab coats, safety glasses, and tying your hair back if it’s long. It is the same as Edna Mode’s “no capes.” Flowing hair looks cool all the way to the explosive ball of flames that engulfs someone’s head.

Viruses are small. You can’t see viruses down a normal microscope—they need a special microscope called an electron microscope. These are highly specialized and take a long time to make the preparations to be able to see the virus. Normally viruses are detected by inference—measuring part of them using an assay that can amplify tiny amounts of material, for example PCR.

Viruses don’t really cause zombie apocalypses. 

Vaccines work. But they take time. The best vaccine in the world will still only prevent infections two weeks after it is given. Drugs are quicker, but still take some time. But the good news is an infection is not going to kill you (or turn you into a zombie) quickly, so they both have time to work.

Scientists use viruses as a vector to introduce healthy genes into a patient’s cells:

Your Fictional Virus & Vaccine

When creating your own fictional virus, research further on the topic and consider choosing a specific one as your basis/inspiration.

Here's one resource. For some of them, you'll need a subscription to access, but those that are available give you a good overview of the virus, as well as treatment options.

You can do the same for creating your fictional vaccine:

Here's one resource. And here's one on vaccine developments.

Sources: 1 2 3 4 5 6 7 8 9 10 11 12 13 ⚜ Writing Notes & References

Lastly, here's an interesting article on how science fiction can be a valuable tool to communicate widely around pandemic, whilst also acting as a creative space in which to anticipate how we may handle similar future events.

Thanks so much for your kind words, you're so lovely! Hope this helps with your writing. Would love to read your work if it does :)

[wachinyeya]

New Safer RNA Insecticide Can Target Only the Devastating Potato Beetles and No Other Bugs https://www.goodnewsnetwork.org/new-safer-rna-insecticide-can-target-only-the-devastating-potato-beetles-and-no-other-bugs/

[cleverwordsandotherstuffilike]

Medical innovations and scientific advances at Harvard Medical School through the decades (Part 2 of 2)

1995 Triple-organ transplant; kidney disease blood glucose levels

1996 How cells sense oxygen; Alzheimer's treatments; immune system advances

1997 p73 gene; aspirin

1998 Adult live-donor liver transplant

1999 Fluorescent molecular probes

2000 Brain abnormalities associated with abuse and neglect

2001 Circadian clock

2002 Rheumatoid arthritis pathway; C-reactive protein

2003 Multi-drug-resistant tuberculosis treatment; source of pre-eclampsia

2004 Blood stem cells; protein transfer

2005 Prenatal nutrition; herpes vaccine candidate

2006 Cholesterol mechanism; DNA sequencing techniques

2007 Cellular switch; rheumatoid arthritis gene; brown-fat cell switch

2008 RIPKI inhibitors; metastatic melanoma remission

2009 LIN28 protein; RNA interference; cancer cells' starvation; brown fat

2010 Enhancer transcription

2011 Kidney failure markers; cancer cell vulnerability; global health care budget models

2012 Tumour suppressor gene p53; ancient migration; infectious disease diagnostics

2013 Cardiac hypertrophy reversal; cathepsin k pathways

2014 Hematopoietic stem cells; pancreatic stem cells

2015 Bioartificial replacement limb; PD-1 pathway; The Lancet Commission on Global Surgery; pseudogene; damaged protein disposal; multiple sclerosis; somatic mutations; deafness gene therapies

2016 Sigma-1 receptor structure; Zika vaccine candidate; circadian rhythm-bipolar disorder link; microbiome

2017 Unlocking the blood-brain barrier; deciphering the structure of a scissor like enzyme

2018 The 'graying' of T cells; From one cell, a detailed road map

2019 Finding herpes' Achilles' heel; viral peptides critical to natural HIV control

2020 How COVID causes loss of smell; obesity fuels tumour growth; heart muscle dysfunction

2021 SARS-CoV-2 vaccine; immune evasion; AI gene interpretation; radiation vulnerability

2022 Fruit fly cell atlas; viral infection on video; boot camp for immune cells

2023 How the brain senses infection; new origin of breast cancer; the microbiome and cancer immunotherapy

[bpod-bpod]

Stopping Sprouts

Like roads in a city, veins in your body need careful mapping. When they don’t stick to the plan, sporadic vascular malformation – malformed veins – occur, causing pain and disfigurement. These veins form lesions containing genetically faulty cells (mutants). Currently, lesions often recur after treatment. Researchers now search for new therapeutics by growing mutant endothelial cells (ECs), collected from the veins of patients, in dishes. RNA sequencing revealed mutant ECs produced the signalling molecule TGFa. Fluorescence microscopy revealed when supporting cells from lesions (stromal cells) were grown alongside normal ECs, they triggered more EC sprouting (pictured, middle, right) compared with non-lesion stromal cells (left). Next, by grafting mutant ECs into mice, they found EC-produced TGFa triggered stromal cells to release the signalling molecule VEGFA. This caused EC sprouting and malformed veins. Treating mice with afatinib, a drug that interferes with VEGF signalling, decreased lesions, suggesting it may be a useful therapeutic.

Written by Lux Fatimathas

Image from work by Suvi Jauhiainen and Henna Ilmonen, and colleagues

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, May 2023

You can also follow BPoD on Instagram, Twitter and Facebook

[farcillesbian]

I love talking to non biologists about my research because I get to think of fun and creative ways to explain oxidative stress or RNA interference or freeze tolerance and usually I'm pretty successful at conveying it and that make me feel good :) a couple weeks ago a sociologist asked me what a model organism is and then why we would want to work with something that isn't a model organism and that was a fun brain exercise too

[falseandrealultravival]

Japan's 30-year recession and innovation (Essay)

Professor Kaliko (m-RNA vaccine inventor)

Since the bubble economy collapsed in the 1990s, Japan has been stuck in a 30-year recession. Workers' wages are shrinking, and Japan is the only developed country in the world to experience subsidence. There are various reasons for this phenomenon, but it is probably due to the government's wrong policies (the Liberal Democratic Party).

What is most troubling to the population is the ultra-low interest rate policy introduced after Abenomics, launched by the exiled politician Shinzo Abe. However, the underlying cause is much deeper. The real culprit is Prime Minister Junichiro Koizumi. This man believed in neoliberalism and applied this false economics to the world of education. -- ``Selection and concentration,'' placing fixed rankings on universities, sparing research funding, and only allowing research that would produce immediate results. Researchers atrophied, and original research faded into obscurity. There are almost no Japanese Nobel Prize winners in science anymore.

This hindered innovation, and Japan no longer developed novel science and technology. Look, isn't the USA, with its active innovation, currently leading the world? The interference of science and technology amateurs in this field is the cause of Japan's current stagnation. Junichiro Koizumi's sin is serious.

Listening to the statements made by the Japanese government, the central bank (Bank of Japan), politicians, and the Japan Federation of Economic Organizations (Keidanren), I find that while they mention money redistribution, they rarely say anything about innovation in science and technology. Today, Japan is dominated by people with liberal arts backgrounds, not science and engineers. Because they are ignorant of science and technology, they have no idea that innovation determines a country's rise and fall. Japan is on the path to becoming a second-rate country. The Bank of Japan now (Head: Kazuo Ueda) is a group of idiots. No matter how much they twist finance, it will not lead to innovation.

Rei Morishita

日本の３０年不況とイノベーション

１９９０年代にバブル経済が破綻して以降、日本は３０年にわたる不況から抜け出せない。労働者の賃金は目減りし、先進国では唯一地盤沈下している。この現象の要因は、いろいろ言われるが、もとは政府＝自民党の誤った諸政策に起因するであろう。

もっとも人口に���炙しているのは、亡国政治家安倍晋三が始めたアベノミクス以降の超低金利性政策だが、深層はもっと根深い。ずばり、真犯人は小泉純一郎首相である。この男は新自由主義の信奉者で、教育の世界にも、この誤った経済学を適用した。――「選択と集中」、大学に固定した順位をつけ、研究費を出し惜しみして、すぐに結果のでる研究しか認めなかった。研究者は委縮し、独創的な研究は影を潜めた。もう、科学におけるノーベル賞受賞者は、日本人からはほとんどでないだろう。

これはイノベーションを阻害し、日本には斬新な科学技術は生まれなくなった。見よ、現在世界をリードしているのはイノベーションが活発なUSAではないか。科学技術の素人がこの分野に口を出したことが今の日本の停滞の元凶なのである。小泉純一郎の罪は重い。

日本の政府、中央銀行（日本銀行）、政治家、経団連の発言を聞いていると、お金の再配分のことは言及しても、科学技術のイノベーションについての発言はほとんどない。今の日本を支配しているのは、理系の科学技術者ではなく、文科系の出身者ばかりである。彼らは科学技術に無知であるから、国の興亡を左右するのがイノベーションであることが全く理解できない。日本は２流国への道をまっしぐらである。日本銀行もバカ集団だ。金融をいくらこねくりまわしても、イノベーションにはつながらない。

[fazedlight]

It's called RNA interference!

[didanawisgi]

How the innate immune system manages to cope with antibody resistant SARS2 varieties

December 17, 2024 Radagast 

"So, as I have been documenting over the past few years now, we’ve seen a situation in which the new coronavirus, SARS-COV-2, become forced to evolve first into increasingly infectious variants (Alpha, Delta) with higher ACE2 affinity and then into highly antibody evasive variants (the Omicron variants). This then results in a population that has a relatively wide range of antibodies, to a wide range of Spike epitopes.

That results in a situation, where SARS-COV-2 becomes increasingly forced to increase its inherent antibody resistance. That involves the accumulation of sugar molecules (glycans) on the N-Terminal Domain, that prohibit the antibodies from binding that are now necessary for neutralization. This interplay between the vaccine, the immune system and the virus, is a process that takes many years to unfold. 

What critical thinkers would ask themselves, is why we don’t just see every virus that regularly reinfects humans develop a bunch of glycans on its surface, if that allows viruses to render an antibody response useless. Logic would suggest there has to be some sort of cost involved for a virus, in covering a viral protein in these glycans that prohibit antibodies from binding to the protein.

This is a correct assessment. The innate immune system evolved various mechanisms to recognize basic patterns that pathogens and misbehaving cells in our bodies tend to display. As one example, our cells are forced to display small bits of proteins they’re producing in their MHC molecule on their surface. This allows your T cells to inspect whether they’re producing the right proteins, or whether their protein factory was hijacked by a virus.

Many viruses thus evolved mechanisms to interfere in this phenomenon, by stopping cells from displaying the MHC molecule on their surface altogether, so that the T cells can’t inspect what’s going on. The human immune system of course has to have ways to deal with that behavior of viruses. So what you see is that our Natural Killer cells, a population part of the innate immune system, treat it as suspicious when a cell fails to produce the MHC molecule, and weigh it as a factor part of their complex calculation on whether a cell should be killed or not.

The innate immune system has various other such clever mechanisms. There are specific molecules it produces, that allow it to recognize proteins that are unusually densely covered in these antibody-blocking glycans. These molecules are called Lectins. Lectins are what we call carbohydrate binding proteins that seek out sugar groups part of bigger molecules.

When it comes to the immune system, C-type Lectins appear to be the most relevant in our defense. These are proteins expressed by most cells part of the innate immune system. There are many different types of C-type Lectins and they tend to look specifically for proteins that have a high density of glycans. 

That is, the recognition is density dependent. A normal protein part of our body may have some glycans, but a very high density of glycans on a protein reveals to the innate immune system that something weird may be going on that requires intervention.

As I have explained a few times before, natural immunity results in the expansion of the population of plasmacytoid dendritic cells, which recognize viral RNA and/or DNA. This is only possible when the first exposure occurs in the absence of an adaptive immune response induced by previous vaccination, as otherwise the B cells will just deal with an infection, before the plasmacytoid dendritic cells ever get to see the virus and proliferate in response.

When the plasmacytoid dendritic cells detect viral RNA/DNA, through their toll like receptors, they start to produce large amounts of Interferon alpha, which is a molecule that evolved to interfere in just about every step of the viral reproductive cycle. However, how much Interferon alpha they produce, is also dependent on secondary factors.

One of these factors, is whether their own specialized C-type lectin receptors like CLEC4C, recognized some protein that’s densely covered in glycans. If that is the case, they boost their interferon alpha production. For the plasmacytoid dendritic cells it becomes easier to realize it’s time to do their job, when the glycan density on the Spike protein starts to increase.

Another place where you see the innate immune system respond differently in breakthrough infections versus natural immunity, is in the brain. What you see here is that a population of monocytes gets to enter the brain upon infection, that does not get to enter the brain if someone was vaccinated before being infected. You also see an increase in Natural Killer cells and Dendritic cells in the brain.

The natural killer cells recognize whether a cell is infected by the virus and then decide whether the infected cells should be killed or not. But the monocytes and the dendritic cells also have an important job: Their job is to “eat” viral particles.

The dendritic cells try to capture viral particles, so that they can then degrade the viral particles with their lysosomes. But how do the denritic cells capture viral particles? They use their C-type lectin receptors for that!

In other words, what you would expect to see, is that as the dendritic cells now become faced with variants of SARS-COV-2 with more glycans on the Spike protein, they start to be able to do their job more effectively.

In essence, what’s currently happening is that SARS-COV-2 is being forced by the mass vaccination experiment, to evolve in a direction that makes it easier for the innate immune system to recognize the virus.

This is good for young people, as their innate immune system tends to be strong and capable. After all, it has to be able to protect them against all sorts of pathogens, as they normally don’t have any adaptive immunity yet against most of the pathogens that circulate (except for the passive adaptive immunity from breastfeeding).

You would expect this to cause problems however, for people whose adaptive immune system is mainly responsible for suppressing this virus. After vaccination, antibody concentration are about fifty times higher than normally seen after infection. 

Constant breakthrough infections have not stimulated innate immunity. Rather, they just recall and broaden the adaptive immune response developed as a consequence of vaccination with non-live vaccines. 

Once antibodies against the Receptor Binding Domain became unable to solve the problem, the immune system developed a type of antibody that targets part of the Receptor Binding Domain and part of the N-Terminal Domain (the N1 loop), to which the virus then responded with BA.2.86, which has a unique insertion mutation exactly in the part where these antibodies bind. 

This BA.2.86 lineage wiped out all other lineages, revealing that most of the world’s population depends very strongly on the antibody response to keep the virus under control. The body then developed antibodies to this new version of the N1 loop, to which the virus then began to respond by putting the glycans on the N1 loop.

This is why you’re dealing with a situation where everyone keeps catching SARS-COV-2 and getting sick as a result. 

All these elegant receptors our innate immune cells have to recognize glycoproteins like the Spike protein, like the C type lectin receptors, tend to depend on the Spike protein not being covered by antibodies. If there are antibodies on the Spike protein, those receptors bump into the antibodies, rather than managing to bind the Spike protein.

This is important to understand: If the antibodies are already on the job, they have to solve the job. And so when the virus has mutated to make the antibodies that bind to it of poor quality and to mainly keep around enhancing antibodies, that bind in places where they won’t stop the Spike protein from correctly binding to the ACE2 receptor, the immune system is forced to start targeting more and more regions of the Spike protein (immune refocusing).

Worst of all perhaps, some of these antibodies directed against SARS-COV-2, seem to cross-react with other respiratory viruses, like Influenza, where they bind to the glycans, but don’t neutralize the protein. So, these antibodies against SARS-COV-2, seem to be making it more difficult for the immune system to deal with other respiratory viruses too, because it’s just much harder for the C-type lectin receptors of the innate immune cells to bind to a protein when it already has these antibodies on it, particularly on its glycans.

You see an epidemic of various respiratory viruses around the world right now, sickening people at abnormally high levels. You need to be asking yourself, what the cause of that is. Some of it may be damage to the immune system, some of it may be due to antibodies against SARS-COV-2 interfering in the innate immune system’s ability to deal with those viruses. I already warned about this long ago.

The point I wish to make clear however with this post, is that it’s inappropriate to expect that the evolution of SARS-COV-2 towards a glycan-covered antibody resistant virus would increase its inherent virulence for everyone.

Instead, what you would expect to see, is that as these glycans accumulate on the Spike protein, the virus will increasingly begin to sicken people who depend on an adaptive immune response against it, whereas when the innate immune system handles the response to this virus, the impact on people’s health will start to decline.

Who cares about any of these details? Well, I’m explaining this for a reason. Immunologists are currently in the process of developing new types of SARS-COV-2 vaccines, that manage to evade recalling the original antigenic sin antibodies and encourage the development of new antibodies instead.

BUT THIS IS THE WRONG APPROACH!

You are very clearly dealing with a virus, that is increasing its glycan density!

And when a virus is rapidly increasing its glycan density, the immune system becomes increasingly dependent on the innate immune response to deal with it, as it just becomes easier to recognize it through the C-type lectins, while the most important parts of the virus for antibody mediated neutralization become inaccessible due to the glycans!

You have to figure out how to suppress the adaptive immune response, allowing the innate immune system to take over and do its job. I have seen just one approach that looks viable to me: Cannabinoids like CBD can suppress adaptive immunity, while encouraging NK cell activity. 

It’s not coincidence, that you see better immunological functioning in HIV infected people with strong cannabis use. You see a DECREASED VIRAL RESERVOIR, in cannabis using HIV infected people. Because HIV rapidly mutates and establishes persistent infections, an antibody response is the wrong tool for the job. HIV already covers itself in a dense glycan shield.

Heavy cannabis use has the effect in HIV infected people of shifting their immune response to HIV more towards dependence on the innate immune system. For a respiratory virus like SARS-COV-2, which is still mostly targeting the lungs of vaccinated people, vaporized cannabis would seem like a proper candidate to me, to reduce the immunological abnormalities that were induced by vaccination. The terpenes are also known to have beneficial stimulating effects on the innate immune system.

Look, I understand this is just a weird blog, but look around you. People are coughing everywhere. They’re collapsing on stage. The hospitals are overwhelmed, there’s an epidemic of “walking pneumonia”, at record levels that have never been seen before since we started measuring in the 90’s. People don’t have to believe me, you can just connect the dots yourself.

This is not just some inherent trait of SARS-COV-2, it is mostly a consequence of provoking an inappropriate immune response towards SARS-COV-2. It really doesn’t have to be like this."

[soumyafwr]

RNA Interference (RNAi) Drug Delivery Market Share, Overview, Competitive Analysis and Forecast 2031

[roshankumar7904800]

Transthyretin Amyloid Cardiomyopathy Market

Transthyretin Amyloid Cardiomyopathy Market Size, Share, Trends: Pfizer Inc. Leads

Emergence of gene silencing therapies reshapes the treatment landscape.

Market Overview: 

The Transthyretin Amyloid Cardiomyopathy Market is projected to grow at a CAGR of 12.5% from 2024 to 2031. The market value is expected to rise significantly during this period. North America currently dominates the market, with key metrics indicating strong growth in innovative treatment options and increasing awareness about this rare disease. The market is experiencing robust expansion driven by advancements in diagnostic technologies, rising prevalence of the disease, and growing investments in research and development of targeted therapies.

The development and application of gene silencing drugs, particularly RNA interference (RNAi) therapy, are altering the treatment choices for transthyretin amyloid cardiomyopathy (ATTR-CM). These innovative medicines aim to reduce transthyretin protein production at the source, perhaps slowing or reversing disease progression. Recent clinical trials have produced promising results, with many gene silencing medicines lowering serum TTR levels and improving cardiac function. During phase 3 trials, a well-known pharmaceutical company discovered that its RNAi therapy reduced serum TTR levels in ATTR-CM patients by up to 80 percent. This trend is expected to continue as novel gene silencing drugs progress through late-stage clinical trials and may reach the market in the coming years.

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Market Trends: 

The development and application of gene silencing drugs, particularly RNA interference (RNAi) therapy, are altering the treatment choices for transthyretin amyloid cardiomyopathy (ATTR-CM). These innovative medicines aim to reduce transthyretin protein production at the source, perhaps slowing or reversing disease progression. Recent clinical trials have produced promising results, with many gene silencing medicines lowering serum TTR levels and improving cardiac function. During phase 3 trials, a well-known pharmaceutical company discovered that its RNAi therapy reduced serum TTR levels in ATTR-CM patients by up to 80 percent. This trend is expected to continue as novel gene silencing drugs progress through late-stage clinical trials and may reach the market in the coming years.

Market Segmentation: 

TTR Stabilisers presently account for about YY% of the Transthyretin Amyloid Cardiomyopathy market. This dominance stems from their shown efficacy in stabilising the transthyretin protein and delaying disease progression. TTR stabilisers were among the first targeted drugs approved for ATTR-CM, and they have demonstrated significant therapeutic benefits in terms of lower mortality and higher quality of life.

A recent long-term follow-up study from a major clinical trial revealed that patients treated with a leading TTR stabiliser experienced a 30% reduction in all-cause mortality over a 5-year period when compared to placebo. The overwhelming evidence has established TTR stabilisers as a critical component of ATTR-CM treatment.

TTR stabilisers have grown in popularity in developed countries, with prescription rates rising by YY% in North America and Europe over the last two years. This growth is being driven by more acceptance of both wild-type and hereditary ATTR-CM, as well as increased clinician knowledge with these drugs.

Market Key Players:

Pfizer Inc.

Alnylam Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Eidos Therapeutics, Inc. (BridgeBio Pharma)

Akcea Therapeutics, Inc.

Intellia Therapeutics, Inc.

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Name: Hari Krishna

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