the vast biotech dilemma

The mRNA so-called “vaccine” has proven to be extremely toxic around the world to many millions of people. The intense multi-dimensioned campaign to push this tech upon the world public and control the narrative in every way at every level of this injection process derived from a deep stealth program wherein world population manipulators from WEF, Gates and their allies in many sectors have dominated. Honest investigation is the only avenue possible to discover how mankind can be released from stealth, from heavy monopolies, from world dictatorship by those with an agenda not of goodwill but often pretending to be “quite caring”. Specifically then the so-called vax has several key scientific design centers (besides the issue of graphene and other bizarre toxins entering in): A) the spike-protein with Crispr gene-editing at a certain point in its synthetic genome has a main root at BioNTech at Mainz, Germany. The other obvious danger point is B) the LNG center at U. of British Columbia, and this involves many recent LNG innovations. Then there is C) the factor of CCP-planned and directed Chinese technicians/scientists seeded throughout the West. The highly specialized Dr. Cui and her team did steal many most- virulent viruses from Canada’s most secure defense laboratory (Winnipeg level 4 national lab) and hastily left Canada for PRC, having been there more than a decade along with her very advanced scientific husband, it is very obvious that every institution in the West doing key tech research are also very exposed by the same method. 150 Chinese nuclear researchers were discontinued from Los Alamos nuclear labs in the last year or two. D) Then the safety testing of the never-ending so vaunted “vax” worldwide by governments and so many scientists connected or not connected to pharma has been exceedingly aborted. So then big media and big tech followed the pattern. How could the public then have much chance of escape from toxic factors? So herein begins deep probing of LNP development at UBC, via open source. -r.: Precision NanoSystems and AbCellera. AbCellera began at UBC in 2012 with only six employees, including founder and now CEO Dr. Carl Hansen—formerly a professor of Physics and Astronomy at UBC. Now the company which pioneered an antibody discovery platform is one of the fastest growing and most valuable biotech companies in Canada, recently partnering with pharmaceutical giant Eli Lilly and Co. to develop an antibody treatment for COVID-19. Precision NanoSystems, developed through a collaboration between Dr. Hansen and Dr. Cullis at UBC, is leveraging its cutting-edge biomanufacturing platform, with support from the federal government, to build one of Canada’s first large-scale manufacturing facilities capable of producing mRNA vaccines and other genetic medicines domestically. The common theme amongst each company? They were all began at UBC, first as research in university laboratories and then as start-up companies. The university provides entrepreneurial support to researchers who have technology determined to have a potentially high societal impact that would be best realized through commercialization. UBC researchers are also creating biotech companies that are helping to drive health innovation and fuel Canada’s economy. For example, Notch Therapeutics, co-founded by Dr. Peter Zandstra, is developing a pipeline of cellular immunotherapies for treating cancer and other diseases and recently raised USD$85 million in venture funding. For UBC Vice-President Health Dr. Dermot Kelleher the pandemic has shone a spotlight on the critical role emerging biotech companies are playing in developing safe treatments for diseases, including COVID-19.
“We still have a long way to go, but the pandemic has demonstrated what can be accomplished at an accelerated pace,” says Dr. Kelleher. “As we turn towards recovery, we have an unprecedented opportunity now to invest in B.C.’s biotechnology sector and to accelerate scientific discoveries into new drugs and treatments more effectively and more efficiently for other diseases such as cancer, diabetes and heart disease.”… For Dr. Pieter Cullis a silver lining of the pandemic is that it has shown how fast new treatments and vaccines can be safely developed with sufficient resources and a sense of urgency. His hope now is to extend Acuitas’ lipid nanoparticle technology, which delivers encapsulated messenger RNA to enter targeted cells, to be able to treat other diseases. He envisions a future in which patients can receive a vaccine to prevent any number of diseases, including cancer.
  https://science.ubc.ca/news/ubc-grown-biotech-leads-global-pandemic-efforts ……………… Development of lipid nanoparticle formulations of siRNA for hepatocyte gene silencing following subcutaneous administration Sam Chen  1 , Yuen Yi C Tam  1 , Paulo J C Lin  1 , Alex K K Leung  1 , Ying K Tam  2 , Pieter R Cullis  3 DOI: 10.1016/j.jconrel.2014.09.025 In summary this work shows that appropriately designed LNP-siRNA systems can result in effective hepatocyte gene silencing following s.c (under the skin) administration. Copyright © 2014 ……………… Effect of Cholesterol Content of Lipid Composition in mRNA-LNPs on the Protein Expression in the Injected Site and Liver After Local Administration in Mice. Kawaguchi M, Noda M, Ono A, Kamiya M, Matsumoto M, Tsurumaru M, Mizukami S, Mukai H, Kawakami S. J Pharm Sci. 2022 Dec ………. Lipid Microparticles Show Similar Efficacy With Lipid Nanoparticles in Delivering mRNA and Preventing Cancer. Ji A, Xu M, Pan Y, Diao L, Ma L, Qian L, Cheng J, Liu M. Pharm Res. 2022 Nov 30:1-15. doi: 10.1007/s11095-022-03445-1 . ……………… Pieter R. Cullis, PhD., FRSC, FNAI (USA) Professor, Department of Biochemistry and Molecular Biology, UBC My research interests concern the roles of lipids in biological membranes and the development of nanomedicines using lipid nanoparticle (LNP) technology to deliver small molecule drugs and macromolecular “genetic” drugs in vivo. Studies on the roles of lipids concern the ability of membrane lipids to adopt non-bilayer structures (including the roles of such structures in processes such as membrane fusion) and transport processes across bilayer lipid systems induced by trans-bilayer ion gradients…. Bin Zhao, BSc, PhD My research interest is concentrated on the development of functional DNA nanostructure-based lipid nanoparticle (LNP) platforms for enhanced and triggered release of therapeutic drugs and nucleic acids. A current project is focused on the use of pH-responsive DNA nanostructures to understand the mechanism whereby LNP are delivering siRNA or mRNA to the cell cytoplasm. https://scholar.google.com/citations?user=nDmhu_EAAAAJ&hl=en Karen Chan, BSc, PhD My research is centered on developing novel lipid nanoparticle (LNP) formulations for the delivery of diverse therapeutic cargo. A current project is focused on the encapsulation of immunomodulatory peptides. I am also interested in the use of LNPs for delivering gene therapy drugs to treat blood coagulation disorders. Miffy Cheng, BSc, PhD My research interest includes the synthesis of new lipid nanoparticle building blocks and developing novel lipid-based nanoparticles platforms. My research also explores the intrinsic physicochemical properties of lipid nanoparticles and incorporates different imaging probes to enable image guidance toward gene therapy and optimally improve gene delivery. researchgate.net/profile/Miffy-Hok-Yan-Cheng Yan Mei, BASc, MASc, PhD My research is focused on optimizing lipid nanoparticle formulations for the delivery of different therapeutic molecules. I am also interested in developing novel trigger release lipid nanoparticle systems to locally control the delivery.   Arash Momeni, BSc, MSc, PhD graduated with BSc and MSc degrees in Biomedical Engineering from Tehran Polytechnic University, working on polymeric and lipid-based drug delivery systems…. moved to Germany with an NSERC postdoctoral fellowship in 2017. In Germany he joined the Biomaterial department of the Max Planck Institute of Colloids and Interface Science and in collaboration with the Max Planck Institute of Molecular Plant Physiology, he focused on nano/micron-scale biomineralization in marine algae, coccolithophores. In 2021 he joined Pieter Cullis lab developing nanoparticles for lipid-based platforms with a triggered release potential. Jerry Leung, BSc (Hons) My research focuses on using lipid nanoparticles to modify platelets and their precursor cells, megakaryocytes, to produce platelets with enhanced and improved functions. Madelaine Robertson, BSc (Hons) My research is focused on optimizing and employing lipid nanoparticles as a delivery system for mRNA and other proteins into platelets. The goal being to express exogenous proteins that could alter platelet function, such as improving clotting ability. Yao Zhang, BSc My research focuses on the formulation and characterization of lipid nanoparticles used for drug delivery. I am also interested in the physiochemical and morphological properties of these systems. Harrison Fan, BASc, MASc The core of my research is focused on the design and assembly of apparatuses to trigger the release of lipid nanoparticle systems. The use of encapsulated magnetic nanoparticles and intense oscillating magnetic fields may be one key technology to assist the localized release of, for example, anti-cancer drugs. Theresa M. Allen, PhD, FRSC
Professor Emeritus, Pharmacology & Oncology, University of Alberta, Edmonton
Co-Founder and Strategic Advisor, Centre for Drug Research and Development (CDRD), Vancouver https://www.liposomes.ca/members/current ……………… The LNP technology was key to the success of COVID-19 shots from Moderna and Pfizer-BioNTech collaboration. But as beneficial as these fats are, there is plenty of room for improvement. The nanoparticles are a major source of unwanted side effects when they spread through the body, triggering the aches and inflammation many people experience after vaccination. They do a poor job of unloading their cargo once inside cells, a necessary step for the protein-making machinery to turn the mRNA sequences into immune-priming signals. And because they tend to fall apart when warm, they have to be stored at low temperatures, limiting their global use. “This is a system that clearly has legs,” says biochemist Pieter Cullis of the University of British Columbia (UBC), Vancouver, who created the first LNPs, but “we still need to increase the efficiency of LNPs—that’s for sure.” A new generation of LNPs with greater potency, fewer side effects, increased stability and more precise tissue-targeting properties is now under development at big pharma and biotech startups. Big money is at stake: these improved nanoparticles could lead to better mRNA vaccines for COVID-19 and other diseases…. “There is still so much optimization and development that needs to happen,” says UBC bioengineer Anna Blakney, co-founder of the RNA vaccine company VaxEquity. And when it comes to understanding how cells interact with the nanoparticles, “it’s just this big question mark,” she adds. One clue emerged earlier this year when Genentech scientists showed how nanoparticles activate a particular inflammatory pathway, the interleukin-1 axis, which is critical to generating protective immune responses but can also spur side effects. Among the LNPs tested, one made with SM-102, an “ionizable” lipid that helps bind and package mRNA into LNPs, proved an especially strong instigator of this pathway. That could help explain why Moderna’s shot, which relies on SM-102, is both highly effective and prone to making people feel icky. The Genentech team did not evaluate the comparable lipid found in the Pfizer-BioNtech vaccine. But Mohamad-Gabriel Alameh and colleagues from the University of Pennsylvania Perelman School of Medicine tested a closely related one and found that it triggered a wide range of inflammatory molecules, both desired and not. The goal now is to design ionizable lipids that activate favorable immune pathways without overstimulating detrimental ones, says Alameh, who co-founded AexeRNA Therapeutics with bioengineer Michael Buschmann of George Mason University and others. “Is it very simple? No,” Alameh says, but it should be possibc…. Sanofi has begun to evaluate some of its customized LNPs head-to-head in human trials. In a study launched in 2021, for example, the company assessed two LNP options for delivering an mRNA flu shot it is developing. According to preliminary data, one lipid formulation proved much better at kick-starting anti-influenza immunity, Frank DeRosa, head of research and biomarkers at Sanofi’s mRNA Center of Excellence, announced at an investor event in December 2021. But the same LNP also provoked more frequent side effects at higher doses. …The heightened focus on LNP technologies, along with the profits reaped from COVID-19 vaccines, has brought increased litigation. Alnylam, which helped develop the first approved medicine delivered in an LNP—a gene-silencing drug marketed since 2018 to treat a rare neurodegenerative disorder—claims that its foundational patents cover lipid components of the Moderna and Pfizer-BioNTech vaccines. https://www.science.org/content/article/better-fat-bubbles-could-power-new-mrna-vaccines …………….…… Thomas D. Madden, Ph.D. President & CEO of Acuitas Therapeutics, Dr. Thomas D. Madden is a world-renowned expert in the area of nanotechnology. Dr. Madden co-founded Acuitas Therapeutics in February 2009 and has guided the company into its position as a global leader through the development and application of lipid nanoparticle (LNP) technology. Acuitas Therapeutics partners with leading pharmaceutical and biotechnology companies and prestigious academic institutions around the world, providing its proprietary LNP delivery technology to enable new drugs based on nucleic acid therapeutics. Recent achievements include the use of its LNP delivery system in the Pfizer/BioNTech COVID-19 vaccine COMIRNATY® that is being administered around the world. This success resulted in the recently announced partnership with Pfizer that enables the American multinational pharmaceutical company to use Acuitas Therapeutics’ LNP technology for up to 10 targets for vaccine or therapeutic development. Under Dr. Madden’s leadership, the team continues their work with partners to address serious illness and diseases such as HIV/AIDS, cancer, tuberculosis, malaria and more. Dr. Madden obtained his BSc. and Ph.D. in Biochemistry from the University of London, U.K. He has held several senior academic and industry positions including Assistant Professor in Pharmacology at the University of British Columbia and Senior Director, Technology Development and Licensing at Tekmira Pharmaceuticals. At Tekmira Pharmaceuticals, Dr. Madden was responsible for the development of several liposomal anticancer agents including Marqibo™ (liposomal vincristine), Alocrest™ (liposomal vinorelbine) and Brakiva™ (liposomal vinorelbine). All of these products were subsequently licensed to Talon Therapeutics. Dr. Madden headed the team that developed the cationic lipid MC3 and the LNP carrier used by Alnylam Pharmaceuticals for Onpattro™. Onpattro™ was approved in 2018 in the U.S. and Europe for the treatment of transthyretin amyloidosis, a rare condition characterized by an abnormal buildup of a protein called amyloid in the body’s organs and tissues. Onpattro™ is the first in a new class of drugs, called RNAi therapeutics, to receive regulatory approval. While Dr. Madden is internationally respected for his professional expertise and achievements, he has also earned a reputation for his collaborative approach. He credits the success of Acuitas Therapeutics and its exceptional standing on the world stage to the team’s commitment to excellence and the company’s culture of cooperation, both internally and externally…. Along with Acuitas Therapeutics’ co-founders (Drs. Pieter Cullis and Michael Hope), Dr. Madden was recognized by the 2022 Governor General’s Innovation Award. They received this prestigious award for their work in developing LNP systems to deliver nucleic acid drugs. https://acuitastx.com/company/thomas-d-madden-ph-d/ ……………… The success of these COVID-19 vaccines is remarkable and was far from guaranteed. mRNA is incredibly delicate. Enzymes in the environment and in our bodies are quick to chop mRNA into pieces, making lab experiments difficult and the delivery of mRNA to our cells daunting. On top of that, mRNA strands are large and negatively charged and can’t simply waltz across the protective lipid membranes of cells. Many scientists thought the technology would never work. “There were many, many skeptics,” says Frank DeRosa, who began working with mRNA in 2008 and is now chief technology officer at Translate Bio, a firm developing mRNA vaccines with Sanofi. “People used to say that if you looked at it wrong it would fall apart.” Luckily, scientists found a solution. To protect the fragile molecule as it sneaks into cells, they turned to a delivery technology with origins older than the idea of mRNA therapy itself: tiny balls of fat called lipid nanoparticles, or LNPs. LNPs used in the COVID-19 vaccines contain just four ingredients: ionizable lipids whose positive charges bind to the negatively charged backbone of mRNA, pegylated lipids that help stabilize the particle, and phospholipids and cholesterol molecules that contribute to the particle’s structure. Thousands of these four components encapsulate mRNA, shield it from destructive enzymes and shuttle it into cells where the mRNA is unloaded and used to make proteins. Although the concept seems simple, perfecting it was far from straightforward. It is a tremendous vindication for everyone working in controlled drug delivery. Robert Langer, chemical engineer, Massachusetts Institute of Technology Over more than 3 decades, promising lipids studied in the lab often failed to live up to their potential when tested in animals or humans. Positively charged lipids are inherently toxic, and companies struggled for years before landing on formulations that were safe and effective. When injected intravenously, the particles invariably accumulated in the liver, and delivery to other organs is still an obstacle. Reliably manufacturing consistent LNPs was another challenge, and producing the raw materials needed to make the particles is a limiting factor in the production of COVID-19 vaccines today. LNP development has been a headache, but without this packaging, mRNA vaccines would be nothing. “It is the unsung hero of the whole thing,” says Giuseppe Ciaramella, who was head of infectious diseases at Moderna from 2014 to 2018. … Giuseppe Ciaramella, former head of infectious diseases, Moderna At the time, scientists were enamored by advances in genetics that were promising to cure diseases by giving someone new genes or turning disease-causing genes off. Figuring out how to deliver these nucleic acid therapies—either DNA or RNA—into cells was a major challenge and required something more sophisticated than a conventional liposome. Cullis knew that adding positively charged lipids to the liposomes would help balance the negatively charged nucleic acids, but there was a problem. “There are no cationic lipids in nature,” Cullis says. “And we knew we couldn’t use permanently positively charged lipids because they are so damn toxic.” Those lipids would rip cell membranes apart, he adds. A solution came from new lipids that were charged only under certain conditions. During the late ’90s and through the first decade of the 2000s, Cullis, his colleagues at Inex Pharmaceuticals, and the Inex spin-off Protiva Biotherapeutics developed ionizable lipids that are positively charged at an acidic pH but neutral in the blood. The group also created a new way to manufacture nanoparticles with these lipids, using microfluidics to mix lipids dissolved in ethanol with nucleic acids dissolved in an acidic buffer. When the streams of those two solutions merged the components spontaneously formed lipid nanoparticles, which, unlike the hollow liposomes, were densely packed with lipids and nucleic acids. The process was simple in theory, but getting the machine to reliably spit out consistent LNPs was difficult…. Pegylated lipids, in which polyethylene glycol (PEG) strands are attached to lipid heads, have several functions in a nanoparticle. PEG helps control the particle size during formulation, prevents the particles from aggregating in storage, and initially shields the particles from being detected by immune system proteins in the body, according to James Heyes, a former Protiva scientist. Heyes is now chief scientific officer of the LNP company Genevant Sciences—a firm with origins in Protiva. But PEG also has liabilities. It prevents LNPs from binding to proteins that help shuttle them into cells. Because PEG extends particles’ life span in the body, the immune system has more time to spot the particles and start mounting an antibody response. And although PEG is found in many cosmetic, drug, and food products, scientists hypothesize that some people could develop antibodies to PEG and that giving those individuals an injection of PEG-coated nanoparticles could trigger an anaphylactic reaction…. A lipid nanoparticle (LNP) contains hundreds of small interfering RNA (siRNA) molecules, each surrounded by ionizable lipids, phospholipids, and cholesterol. The outside of the particle is coated in pegylated lipids. LNPs for messenger RNA (mRNA) are made with similar ingredients but contain only a few mRNA strands. “A lot of work has gone into studying what happens inside a cell, but trying to understand the transport that occurs before these nanoparticles reach their cells is another question entirely,” says Kathryn Whitehead, a nanoparticle scientist at Carnegie Mellon University. As a consequence, “we don’t even screen in vitro anymore,” she says. “I find it more informative to test directly in an animal.” Even some of the LNPs that worked well in animals proved too toxic for the repeated dosing required of many siRNA therapies. “The biggest issue was trying to find the right balance between systems that were effective but also safe and tolerable,” says Marian Gindy, executive director of pharmaceutical sciences at Merck & Co., who led the RNA formulation team from 2008 until Merck ended its siRNA programs in 2013. “And I would say that is still the biggest challenge in this area.” For a brief time new work on LNPs fell out of favor—that is, until new companies that were focused on mRNA brought fresh energy to the field. BioNTech, founded in 2008, and Moderna, founded in 2010, promised to be able to use mRNA to produce any protein in the body, as either a therapeutic or a vaccine. In the past decade, mRNA garnered billions of dollars of investment. Discovering how to deliver those mRNA strands into cells was a problem from day 1, but prior experience with siRNA provided a launching pad. “Early on people recognized that the same lipids used for siRNA could also be useful for mRNA,” says Daniel Anderson, a nanomedicine and biomaterials scientist at MIT. His group began collaborating with the rare-disease company Shire Pharmaceuticals to encapsulate mRNA that encoded protein therapies to treat rare liver diseases….The off-the-shelf LNP formulations designed for siRNA worked for mRNA occasionally but not very well, says Romesh Subramanian, who led a team at Alexion Pharmaceuticals that worked on mRNA therapies with Moderna from 2014 to 2017. siRNA molecules are like short rods, with two rows of about 20 nucleotides each, he explains. mRNA, in contrast, can easily span thousands of nucleotides, wind into complex shapes, and change the properties of the LNP in ways that are hard to predict. After realizing that MC3 wouldn’t cut it for mRNA delivery, Moderna invested significant resources into building a better ionizable lipid. “There was a group of chemists put on this right away to build novel cationic lipids,” says Ciaramella, the former head of infectious diseases at Moderna. “It is kind of like a small-molecule drug discovery engine, but on steroids….The devil is absolutely in the details as far as LNPs are concerned,” Ciaramella says. “But once you optimize it for one organ, you can change out the mRNA with minimal optimization.” https://cen.acs.org/pharmaceuticals/drug-delivery/Without-lipid-shells-mRNA-vaccines/99/i8 …………..…… Conclusion: biotech/nanotech/genetic engineering is dual use (like bioweapons), but the world population is not much aware of this. LNP development in China is exploding along with CCP intent to be world leader in pharma and other fields. I mention then Sinopeg of Shanghai, the partner of BioNTech which is Fosun Pharma of Shanghai, and then there is very large WuXi Biologics now partnered in a 20-year alliance to an unspecified Western pharma world-leader. It is not pretty mostly an undeclared world war spearheaded by biotech. - regards, r., siskiyou county, california