Marc Grey
Many of the covid vaccines are made using completely new medical tech involving the use of genetic material instead of proteins from the appropriate virus. This has led to them being described as ‘gene therapies not vaccines’ in some circles. In this article, we discuss these new medical technologies and their relationship (or not) to vaccines, and indulge in some speculation about possible future applications.
Firstly, what new medical tech are we talking about? These are two different technologies that achieve that same thing: delivering genetic instructions rather than actual proteins to our bodies.
The first is usually called ‘viral vector‘, and involves modifying a (usually mild or benign) virus by stripping out its genetic material (typically RNA) and replacing it with DNA for the desired treatment protein or proteins. These modified viruses are injected into the body where they attach to cells and inject the DNA. This is taken into the cell’s nucleus, transcribed into mRNA, which in turn is taken back into the cell, read by the ribosomes which finally make the proteins.
The second is usually (confusingly) just called ‘mRNA’ or sometimes ‘mRNA therapeutics‘. This involves embedding messenger RNA (mRNA) that code for the treatment proteins into tiny fatty lumps (lipid nanoparticles). These are injected into the patient where they are small enough to enter cells and from there get read by the ribosomes which make the proteins. A better name for this method might be ‘lipid vector’ as it is the nanoparticle that actually gets the genetic material into the cell, but this term is not in use.
So are these medical technologies gene therapies? They clearly involve placing genetic material into the patient’s body. However, a stricter definition implies that a ‘gene therapy’ is a treatment that is intended to change the patient’s DNA. In the most well-known examples to date (vaccines), the intent is to produce a protein that is part of a virus in order to provoke an immune response, not change the genetic makeup of the patient (there is some controversy and a lot of unknowns about whether the vaccines might – perhaps unintentionally – change the patient’s DNA; let us park that discussion for now). However, it is certainly possible to use these (particularly viral) vectors to make a treatment that does intentionally change a patient’s DNA so overall it is fair to say that these technologies can in fact be considered gene therapies.
What about the Covid vaccines then; does that mean they are not vaccines at all? The best way to understand this question is to note that these technologies were originally created to research treatments and cures for diseases. While work for those is ongoing, the first products using this technology happen to be vaccines: for Ebola (viral vector) and Covid (viral vector and mRNA). So the answer to the question is really that those Covid vaccines are specific examples of this gene therapy technology, but are nonetheless vaccines as they provoke the creation of neutralising antibodies for SARS-CoV-2.
But are the vaccines any good? Initially, it looked like they were (efficacy 80-95%), but real-world numbers with the delta variant are more like 39% in some cases. The rushed nature of the worldwide rollout raised questions about safety (that are still not adequately answered). There was also uncertainty about if they stopped transmission – but now there is quite a lot of data that show that at least some of the vaccines do not prevent transmission.
This is unusual, as the ‘flu vaccine for example does prevent it. This has led to the idea that the cause of this failing is due to the use of the novel gene therapy tech. While that certainly might be the case, it could also be the particular choice of the piece of virus protein coat to use as vaccine material (i.e. the spike protein). We will get to test this theory when the Novavax Covid vaccine gets rolled out, as it uses the spike protein, but is not created using these gene technologies (it is a subunit vaccine that contains the spike protein itself – similar to this year’s ‘flu vaccine). If it also does not prevent transmission then we’ll know that it is the spike protein that is the issue. If it does prevent transmission then some serious questions will need to be asked about the gene therapy based vaccines!
What are these other treatments that have been alluded to? Early research on viral vectors was trialling them for treatment of immunodeficiency, hemophilia and various cancers. Initial attempts at using mRNA methods were severely hampered by the RNA itself provoking an immune response, and it wasn’t until 2011 that Moderna and later AstraZeneca started to develop treatments for cardiovascular, metabolic, renal diseases, and some cancers. An interesting new treatment/vaccine is a personalised ‘vaccine’ that creates antibodies that target the cancer mutations specific to a patient.
If it were not for the arrival of Covid 19 these companies might have stayed focused on this type of research but Operation Warp Speed provided large amounts of funding to switch to Covid vaccine development. Another factor slowing the appearance of these types of treatments is that they are considerably more complex and ambitious than vaccine creation!
Finally, let us indulge in some speculation about other applications for these genetic therapies. The key point to consider is that the DNA or mRNA ‘payload’ can code for any proteins, which opens up many possibilities! There is an example shown to us in the movie ‘The Bourne Legacy’, where a character has had changes made to his mitochondrial DNA that increase the energy output of the mitochondria itself (it is implied that this makes him stronger and more able to endure). Also, the discussion makes it plain that a viral vector was used to achieve this. Is this possible, or just pure science fiction? Well, it is clearly possible – the hard parts are knowing which bits of the DNA (i.e. which genes) to change, and (particular to this case) ensuring that the mitochondrial DNA is changed, not that of the cell itself (mitochondria have their own DNA).
The problem of what genes control which characteristics is complex. We have quite good knowledge of which genes are involved in many pathologies, but very little about which genes might (say) cause social dominance or a muscular build. However, research into the gene-to-characteristics mapping is being done.
With that thought in mind consider two highly speculative examples. Suppose after extensive research a scientist discovers that a set of 6 genes determine the ‘agreeability’ of a human. This raises the possibility of creating a ‘treatment’ that makes people more malleable and easily controlled. It is left to the reader’s imagination to think about what sort of governments and organisations would want to do such a thing…
For the second such example, suppose that a scientist discovers that a set of 4 genes control muscle mass predisposition, and at the same time another one finds that a set of 5 genes controls bone density. This creates the possibility for a ‘treatment’ that makes a ‘super soldier’ caste (this treatment would probably need to be administered at a young age).
Science fiction? Sure, right at this minute. Is research along these lines being carried out by military black projects? Or perhaps are certain ‘philanthropic’ NGOs funding it? Good questions.
