DNA from virus vector vaccines always integrate into the genome of the infected cell. SARS-CoV-2 mRNA from mRNA vaccines would also be able to integrate human genome.

Last update and review: September 7, 2021.

A short summary.

Ugur Sahin and Ozlem Tureci further in their 2014 paper (2) describe the existing regulatory framework for gene therapies and point out the risks associated with the use of viral vector vaccines and DNA plasmids. Since their own product, an mRNA vaccine, can also integrate into the host cell genome, the same strict safety requirements should apply to their vaccine as well. However, nothing of what the regulatory framework, and, frankly, Common Sense require had been done before the vector vaccines based on DNA-viruses and mRNA vaccines were authorized and administered to hundreds of millions. Most of the required safety measures specific to gene therapies are NOT deployed anywhere in the world. How come?

Also, comments of vaccines safety, effectiveness, COVID-19 epidemiology, and effective prevention and treatment measures.

Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues – a study by Zhang et al., 2021 (1).

Who are the authors of this work and who financed it?

The authors work at the following relatively credible institutions:

Whitehead Institute and Massachusetts Institute of Technology (MIT)

HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute

Department of Biology, Massachusetts Institute of Technology.

The authors thank those who provided help. Those who provided help, also work at relatively credible institutions:

Zhang et al., 2021 (1):

“We thank members in the laboratories of R.J. and R.A.Y. and other colleagues from Whitehead Institute and Massachusetts Institute of Technology (MIT) for helpful discussions and resources. We thank Thomas Volkert and staff from the Whitehead genomics core, and Stuart Levine from the MIT/Koch Institute BioMicro center for sequencing support. We thank Lorenzo Bombardelli for sharing protocol and advice for Tn5 tagmentationmediated integration enrichment sequencing. We thank Jerold Chun, Inder Verma, Joseph Ecker, and Daniel W. Bellott for discussion and suggestions.”

The work of Zhang et al., 2021 (1), was financed by The National Institute of Health and other donors.

Zhang et al., 2021 (1):

“This work was supported by grants from theNIH to R.J. (1U19AI131135-01; 5R01MH104610-21) and by a generous gift from Dewpoint Therapeutics and from Jim Stone. S.H.H. was supported by the Intramural Research Program of the Center for Cancer Research of the National Cancer Institute.”

What did the authors, Zhang et al., 2021 (1), found?

“We found that DNA copies of SARS-CoV-2 sequences can be integrated into the genome of infected human cells.”

Zhang et al., 2021 (1):

“Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and recurrence of PCR-positive tests have been widely reported in patients after recovery from COVID19, but some of these patients do not appear to shed infectious virus. We investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the DNA of human cells in culture and that transcription of the integrated sequences might account for some of the positive PCR tests seen in patients. In support of this hypothesis, we found that DNA copies of SARS-CoV-2 sequences can be integrated into the genome of infected human cells.”

“We also found, in some patient-derived tissues, evidence suggesting that a large fraction of the viral sequences is transcribed from integrated DNA copies of viral sequences, generating viral–host chimeric transcripts.”

Zhang et al., 2021 (1):

“We also found, in some patient-derived tissues, evidence suggesting that a large fraction of the viral sequences is transcribed from integrated DNA copies of viral sequences, generating viral–host chimeric transcripts. The integration and transcription of viral sequences may thus contribute to the detection of viral RNA by PCR in patients after infection and clinical recovery. Because we have detected only subgenomic sequences derived mainly from the 3′ end of the viral genome integrated into the DNA of the host cell, infectious virus cannot be produced from the integrated subgenomic SARS-CoV-2 sequences.”

Physiological Literacy: RNA of retroviruses and DNA of DNA viruses ALWAYS integrate into the genome of the infected cell.

Katsura, 2019:

“5-8%(of human genome) is derived from viral sequences similar to infectious retroviruses. If integration of retrovirus occurs in germline, the integrated sequences are heritable.”

Moller et al., 2020:

“Replication of the majority of RNA viruses takes place solely in the cytoplasm, with the exception of retroviruses, which, using reverse transcription, create a DNA provirus in the nucleus of the host cell, that is ultimately incorporated into the genome of the host.”

“Nonretroviral RNA virus sequences have been detected in the genomes of many vertebrate species.”

Zhang et al., 2021 (1):

“One possible explanation for the continued detection of SARS-CoV-2 viral RNA in the absence of virus reproduction is that, in some cases, DNA copies of viral subgenomic RNAs may integrate into the DNA of the host cell by a reverse transcription mechanism. Transcription of the integrated DNA copies could be responsible for positive PCR tests long after the initial infection was cleared. Indeed, nonretroviral RNA virus sequences have been detected in the genomes of many vertebrate species (25, 26), with several integrations exhibiting signals consistent with the integration of DNA copies of viral mRNAs into the germline via ancient long interspersed nuclear element (LINE) retrotransposons (reviewed in ref. 27).”

Nonretroviral RNA viruses such as vesicular stomatitis virus or lymphocytic choriomeningitis virus (LCMV) can be reverse transcribed into DNA copies and DNA copies of the viral sequences have been shown to integrate into the DNA of host cells.

Zhang et al., 2021 (1):

“Furthermore, nonretroviral RNA viruses such as vesicular stomatitis virus or lymphocytic choriomeningitis virus (LCMV) can be reverse transcribed into DNA copies by an endogenous reverse transcriptase (RT), and DNA copies of the viral sequences have been shown to integrate into the DNA of host cells (28–30).”

Biontech founders Sahin and Tureci make errors in their 2014 paper (2), when they state: “mRNA-based therapeutics, unlike plasmid DNA and viral vectors, do not integrate into the genome and therefore do not pose the risk of insertional mutagenesis”.

Ugur Sahin (founder of Biontech, today at Pfizer-Biontech), Katalin Karikó (employee of Biontechin 2014), and Özlem Türeci (founder of Biontech, today at Pfizer-Biontech), 2014 (2):

“Conceptually, there are several important differences between IVT mRNA-based therapeutic approaches and other nucleic acid-based therapies. IVT mRNA does not need to enter into the nucleus to be functional; once it has reached the cytoplasm the mRNA is translated instantly. By contrast, DNA therapeutics need to access the nucleus to be transcribed into RNA, and their functionality depends on nuclear envelope breakdown during cell division. In addition, IVT mRNA-based therapeutics, unlike plasmid DNA and viral vectors, do not integrate into the genome and therefore do not pose the risk of insertional mutagenesis.”

Photo: Biontech founders Ugur Sahin and Özlem Tureci. Biontech contributed to the creation of Pfizer mRNA vaccine against COVID-19.

Sahin and Tureci, founders of Biontech in 2014: DNA-adenoviruses ( used as vectors in Astra-Zeneca-Oxford, Johnson and Johnson, Sputnik and other vector vaccines against SARS-CoV-2) pose a risk of insertional mutagenesis.

Ugur Sahin and his coworkers at Pfizer-Biontech are wrong in the passage cited above. Indeed, mRNA can integrate human genome. There is, however, an important fact in the citation above. That is, DNA-adenoviruses, used as vectors in Astra-Zeneca-Oxford, Johnson and Johnson, Sputnik and other vector vaccines against SARS-CoV-2, pose a risk of insertional mutagenesis.

An increased risk of autoimmunity.

Only a small fraction of the cells in patient tissues express viral proteins but this could trigger conditions such as autoimmunity as has been observed in some patients.

Zhang et al., 2021 (1):

“Do integrated SARS-CoV-2 sequences express viral antigens in patients and might these influence the clinical course of the disease? The available clinical evidence suggests that, at most, only a small fraction of the cells in patient tissues express viral proteins at a level that is detectable by immunohistochemistry. However, if a cell with an integrated and expressed SARS-CoV-2 sequences survives and presents a viral- or neoantigen after the infection is cleared, this might engender continuous stimulation of immunity without producing infectious virus and could trigger a protective response or conditions such as autoimmunity as has been observed in some patients (62, 63).”

Some believe that Pfizer-Biontech or Moderna mRNA vaccines are “less dangerous” because they do not code for full-length spike protein. Is this true?

Pfizer-BioNTech COVID-19 Vaccine encodes a full-length Spike-protein of SARS-CoV-2.

Pfizer-BioNTech in the Briefing Document submitted to the “Vaccines and related biological products advisory committee for the meeting” for the December 10, 2020, meeting (3):

“The Pfizer-BioNTech COVID-19 Vaccine encodes a membrane-anchored, full-length S protein with two point mutations to proline within the central helix domain to lock S protein in an antigenically preferred prefusion conformation.”

“Figure 1.” Vaccine design and characterisation of the expressed antigen, full-length Spike-protein of SARS-CoV-2.

Spike-protein structure in BNT162b2 (Pfizer-Biontech vaccine).

Vogel et al., 2020 (pre-print) (4):

“a, BNT162b2 RNA structure. UTR, untranslated region; S, SARS-CoV-2 S glycoprotein; S1, N-terminal furin cleavage fragment; S2, C-terminal furin cleavage fragment; RBD, receptor-binding domain. Positions of the P2 mutation (K986P and V897P) are indicated.”

Atomic model of Spike-protein structure in BNT162b2 (Pfizer-Biontech vaccine).

Vogel et al., 2020 (pre-print):

“c, A 3.29 Å cryoEM map of P2 S, with fitted and refined atomic model, viewed down the three-fold axis toward the membrane.”

Moderna’s mRNA vaccine is a “single-stranded, 5’-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2” (2).

“One dose (0.5 mL) contains 100 micrograms of messenger RNA (mRNA) (embedded in SM-102 lipid nanoparticles). Single-stranded, 5’-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2. For the full list of excipients, see section 6.1.”

What should have been done prior to the authorization of vector vaccines and mRNA vaccines? And should they have been authorized at all?

Ugur Sahin and Ozlem Tureci further in their 2014 paper (2) describe the existing regulatory framework for gene therapies and point out the risks associated with the use of viral vector vaccines and DNA plasmids. Since their own product, an mRNA vaccine, can also integrate into the host cell genome, the same strict safety requirements should apply to their vaccine as well. However, nothing of what the regulatory framework, and, frankly, Common Sense require have been done before the vector vaccines based on DNA-viruses and mRNA vaccines were authorized and administered to hundreds of millions. Most of the required safety measures specific to gene therapies are NOT deployed anywhere in the world. How come?

The regulatory framework and Common Sense require “to test for genome integration, germline transmission, genotoxicity or carcinogenicity of IMPs (investigational medicinal products), or carry out long-term observation of patients in clinical studies.”

The regulatory framework (and Common Sense) requirements are cited below, from the same paper by the Biontech founders (2).

Ugur Sahin, Katalin Karikó, Özlem Türeci, 2014 (2):

“to test for genome integration, germline transmission, genotoxicity or carcinogenicity of IMPs (investigational medicinal products), or carry out long-term observation of patients in clinical studies.”

Of note: The European Medicines Agency (EMA), rather arbitrarily, excluded vaccines from the category of gene therapy products.

In vivo administered mRNA drug products are presumably viewed as an added recombinant nucleic acid complying with the EU definition of a gene therapy product. But the European Medicines Agency (EMA), rather arbitrarily, excluded vaccines from the category of gene therapy products.

The European Medicines Agency (EMA)’s regulation for advanced therapy medicinal products (Directive 2009/120/EC) as cited by Ugur Sahin, Katalin Karikó, Özlem Türeci, 2014 (2):

“Gene therapy medicinal product means a biological medicinal product which has the following characteristics: “(a) it contains an active substance which contains or consists of a recombinant nucleic acid used in or administered to human beings with a view to regulating, repairing, replacing, adding or deleting a genetic sequence; (b) its therapeutic, prophylactic or diagnostic effect relates directly to the recombinant nucleic acid sequence it contains, or to the product of genetic expression of this sequence. Gene therapy medicinal products shall not include vaccines against infectious diseases.”

The average member of public has been brainwashed into believing that vaccines are almost harmless and provide almost perfect protection from disease. This is far from the truth. Vaccines are risky and their effectiveness is limited.

The average member of public, or should we write, the average member of populace, has been brainwashed into believing that vaccines are almost harmless inert particles, and that they are almost perfectly protect from the target disease. Is this true?

The subject of vaccines safety and effectiveness is vast. We do not want to make this article endless. Very briefly, vaccines are not safe and their effectiveness is limited. “Immunity” itself, whether it results from vaccination or prior infection, is not a perfect protection either.

“Vaccine-enhanced disease”: Any type of vaccine or previous infection may result in complications or enhanced disease. The key points:

“Administration of formalin-inactivated, DNA-based, RNA-based, VLP-based and MVA-vectored vaccine candidates against SARS-CoV has resulted in complications—such as liver damage or increased infiltration of eosinophils into the lung.”

“Vaccine-enhanced disease”.

“Under the appropriate conditions, enhanced disease can be induced in animal models as a result of natural infection or vaccination.”

“Monitoring for the occurrence of this phenomenon (enhanced disease) both during the development of and after the licencing of vaccines is paramount, especially after antibody titres start to decrease.”

Krammer, 2020 (5):

“Although enhanced disease is usually associated with flaviviruses, pre-existing immunity induced by natural infection with or by vaccination against feline coronavirus can lead to antibody-dependent enhancement of disease. This occurs mostly under experimental conditions and seems to be rare in the field 88 . In several different animal models, the administration of formalin-inactivated, DNA-based, RNA-based, VLP-based and MVA-vectored vaccine candidates against SARS-CoV has resulted in complications—such as liver damage or increased infiltration of eosinophils into the lung (suggesting a TH2-type immunopathology)—after challenge with the virus 89–92 . It has been speculated that enhanced disease is driven by non-neutralizing antibodies to the spike protein, but it has also been shown to be triggered by vaccines based on the nucleoprotein 90,93,94 . Bona fide antibody-dependent enhancement of SARS-CoV—even by neutralizing antibodies—has been shown in vitro, although the same antibodies were then found to be protective in vivo 95 . In addition, several vaccine candidates against SARS-CoV induced protective immunity in animal models without signs of enhanced disease. Enhanced disease has also been reported in rabbits after natural infection and re-challenge with MERS-CoV in the absence of neutralizing antibodies 96 . Mice that had been administered an inactivated MERS-CoV vaccine and were then challenged with infectious virus showed enhanced infiltration of eosinophils into the lung despite the presence of neutralizing antibodies. Notably, as with many SARS-CoV vaccines, the virus was better controlled in these mice than in those from the control group 97 . The mechanism behind this phenomenon is still unclear and the data are inconclusive. In this context it is also important to note that enhanced disease is not necessarily a result of antibody-dependent enhancement and could also be induced by other mechanisms. It seems that, under the appropriate conditions, enhanced disease can be induced in animal models as a result of natural infection or vaccination. However, even in animal models of SARS-CoV-2 infection there is currently no evidence for enhanced disease. Nevertheless, monitoring for the occurrence of this phenomenon both during the development of and after the licencing of vaccines is paramount, especially after antibody titres start to decrease.”

Conclusions: it is possible to avoid getting infected; good nutritional status is protective; there are effective prophylaxis measures; there are effective early treatments. Avoiding pathogens is a Life-long skill of intelligent people.

A screenshot of the situation with total cases of SARS-CoV-2 infection as of June 28, 2021. In almost all the countries, 85% of the population avoided getting infected by that point in time.

So far, about 80% of the population in any given country have avoided getting infected. Now, that the limited effectiveness of the current vaccines is an obvious fact, people will start being careful again. It is, therefore, possible that 70% of the population will never be infected with SARS-CoV-2. Thanks to prevention, hygiene measures, smarter people will avoid a number of other pathogens that are circulating and have the same mortality rates that SARS-CoV-2 infection.

Learn to avoid pathogens, be literate, think independently, identify reliable source and trustful advisers.

As a bonus for those who have read this far: nasal “lavages”, or nasal irrigation, is a very effective protective measure. Maybe even “the ultimate protective measure” against air-born respiratory pathogens. Indeed, undiluted humans saliva apparently prevents binding of SARS-CoV-2 Spike-protein to cells. This effect may be mediated by mucins or by high levels of nitrogen oxide in saliva. Mucins are also produced by mucosa of nasal cavity. There are also ways to stimulate nitrogen oxide production in the nose. Just beware that a majority of products negatively affect mucociliary clearance and/or ciliary beat frequency.

A side note: If you need help with the subjects discussed in this article or other advice on health and longevity, do not hesitate to get in contact with us.

Selected references:

1. Zhang et al. Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues. PNAS2021 Vol. 118 No. 21 e2105968118

2. Ugur Sahin, Katalin Karikó, Özlem Türeci. mRNA-based therapeutics — developing a new class of drugs. . Nat Rev Drug Discov. 2014 Oct;13(10):759-80. doi: 10.1038/nrd4278. Epub 2014 Sep 19. PMID: 25233993.

3. Pfizer-BioNTech in the Briefing Document submitted to the “Vaccines and related biological products advisory committee for the meeting” for the December 10, 2020, meeting.

4. Vogel, Tureci (Biontech founder), et al. A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates. A pre-print posted on September 8, 2020.

https://doi.org/10.1101/2020.09.08.280818

Accessed on September 7, 2021.

5. “Summary of product characteristics, Annex 1,” of the Moderna mRNA vaccine as published on the site of the European Medicine Agency available at

https://www.ema.europa.eu/documents/product-information/spikevax-previously-covid-19-vaccine-moderna-epar-product-information_en.pdf – Accessed on September 1, 2021.

The main site with the vaccine information:

https://www.ema.europa.eu/en/medicines/human/EPAR/spikevax#product-information-section