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Depending on the definition, they are or aren't. There seems to be a disagreement. https://www.google.com/amp/s/www.swfinstitute.org/news/83947...



The NHS article states "The mRNA from the vaccines does not enter the cell nucleus or interact with the DNA at all, so it does not constitute gene therapy."

The article you have posted explains what gene therapy is confidently, but it doesn't explain, or reference particularly well, why an mRNA would be considered gene therapy or why it would alter genes.


We should strive to take jthedisciple’s comments at face value, and literally. From there we will arrive at a charitable interpretation.

Here is an example where Harvard Stem Cell Institute discusses mRNA therapy as gene therapy: https://hsci.harvard.edu/translation/what-are-drugs-4-gene-t...

The Wikipedia entry on gene therapy discusses mRNA therapy under the Non-viral section: https://en.wikipedia.org/wiki/Gene_therapy“BioNTech, Moderna Therapeutics and CureVac focus on delivery of mRNA payloads, which are necessarily non-viral delivery problems.”

Indeed the mRNA vaccines carry a genetic payload – a segment of viral genome which is modified using a genetic perspective and from a position of genomic understanding. mRNA is a temporary and deliberately non-permanent message carrier substrate; Here too, humanity’s employment of such facts can be interpreted as scientific knowledge of the matters of the genes. If we choose to call mRNA vaccines gene therapy – which they are less clearly than other techniques – then it is certainly the better gene therapy for purposefully avoiding permanent alteration of the genome in the subject to be treated.


> Here is an example where Harvard Stem Cell Institute discusses mRNA therapy as gene therapy: https://hsci.harvard.edu/translation/what-are-drugs-4-gene-t...

And the very next paragraph (in its heading, no less) makes it clear that RNA therapies and gene therapies are distinct, i.e. that RNA therapies are not (necessarily) gene therapies.

The Wikipedia article you cite doesn’t mention mRNA vaccines. The single mention of “mRNA payloads” does not necessarily refer to vaccines (there are other RNA therapies, and some of these might be gene therapies, although I don’t think they are) — but even if it did the sentence’s inclusion in this article is debatable at the very least.

Fundamentally, gene therapies always work by modifying the host genome. mRNA vaccines don’t do this (nor do any other RNA therapy approaches that I’m aware of).


I assure you thay we are in technical agreement! I’d like to point towards my words on mRNA vaccines precisely and purposefully not modifying the genome.

Re. this: ” And the very next paragraph (in its heading, no less) makes it clear that RNA therapies and gene therapies are distinct, i.e. that RNA therapies are not (necessarily) gene therapies.”

For the avoidance of doubt and my greater understanding, may I ask for a quote of paragraph being referred to?

Edit, update: That paragraph aside, the article index does indeed distinguish between RMA therapy and gene therapy: https://hsci.harvard.edu/translation/what-are-drugs


Title: “Manufacturing gene and RNA therapies” “A challenge for both gene and RNA therapies is getting the nucleic acid molecules into a cell. […]”


Thank you! I want to explicitly state my agreement, due to the sensitivity of nuance here.


No, it doesn’t depend on the definition. This isn’t a point of contention amongst experts. The article you cite is simply wrong (in particular, its claim about the classification of mRNA vaccines as gene therapy in Europe is categorically false), it fundamentally misunderstands how mRNA vaccines work, and it misrepresents the sources it cites supposedly in support.


The swfinstitute.org link aside, there are different ways to define the term. It isn’t jthedisciple who is making the definition; It is a simple fact that there are two major definitions on the Wikipedia entry for gene therapy:

Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect [1] or the treatment of disease by repairing or reconstructing defective genetic material. [2]https://en.wikipedia.org/wiki/Gene_therapy

[1] – Kaji, Eugene H. (7 February 2001). "Gene and Stem Cell Therapies". JAMA. 285 (5): 545–550. https://doi.org/10.1001%2Fjama.285.5.545 – ISSN 0098-7484. PMID 11176856.

[2] Ermak G (2015). Emerging Medical Technologies. World Scientific. ISBN 978-981-4675-81-9

mRNA vaccines are certainly a more ambiguous fit under the term “gene therapy”, but it can be parsed as such that they are a genetic modification of a viral cell to produce a therapeutic effect. With slightly more ambiguity but not at all without reason, we can parse mRNA vaccines as “the treatment of disease by reconstructing genetic material”. Even if the definition includes the word “defective”. To me the crux of the statement does not appear in the genetic material needing to be “defective”. Via metaphor: We may be unprotected from the elements by our shelter being defective, but it may also occur that shelter is simply missing, such as our immune response to SARS-CoV-2.

I personally wouldn’t call mRNA vaccines gene therapy, but it’s more because it can induce misunderstandings on permanence rather than because of the un-parseability of the smaller term under the larger definition.


> It is a simple fact that there are two major definitions on the Wikipedia entry for gene therapy:

I read this as a single definition rather than two distinct ones but, regardless of how you read this, mRNA vaccines do neither of these two things.

> it can be parsed as such that they are a genetic modification of a viral cell

No, it cannot be parsed like this. “Genetic modification” has a specific, technical meaning and mRNA vaccines do not perform it. Furthermore, I’m not even sure what you mean by “viral cell”, since viruses don’t form cells (they form virions). Do you mean a host cell infected by a virus? Because that doesn’t apply here: mRNA vaccines don’t specifically act on infected cells, they act on healthy cells.

> we can parse mRNA vaccines as “the treatment of disease by reconstructing genetic material”

Again, we cannot do this, because it’s flat out incorrect. What does “reconstructing genetic material” even mean in this context? There’s no defect, so there’s nothing to reconstruct, and the mRNA vaccine does not do so anyway since, again, it does not modify the host genome.

— In general I’ll note that several sentences in your answer simply make no biological sense and use made-up terms.


>> it can be parsed as such that they are a genetic modification of a viral cell

> No, it cannot be parsed like this. “Genetic modification” has a specific, technical meaning and mRNA vaccines do not perform it. Furthermore, I’m not even sure what you mean by “viral cell”, since viruses don’t form cells (they form virions). Do you mean a host cell infected by a virus? Because that doesn’t apply here: mRNA vaccines don’t specifically act on infected cells, they act on healthy cells.

I was ambiguously referring to virions as viral cells. Better I hadn't! - thank you - but I think I can be understood nonetheless.

A modification in the frame of mind of genetic understanding is performed on a viral cell. The modification is done from the perspective of an understanding of how genes, genetic material, and genetic processes such as transcription and protein encoding work. A segment of viral genome which encodes part of the body viral is excised and modified.

Then, carried on this understanding, a therapeutic effect is produced.

>> we can parse mRNA vaccines as “the treatment of disease by reconstructing genetic material”

> Again, we cannot do this, because it’s flat out incorrect. What does “reconstructing genetic material” even mean in this context? There’s no defect, so there’s nothing to reconstruct, and the mRNA vaccine does not do so anyway since, again, it does not modify the host genome.

Indeed if you review my words you'll note that I explicitly address the lack of a defect.

The mRNA vaccines we know today can certainly be viewed as a modification and reconstruction of viral genomic material. Of viral RNA genes. Per Wikipedia: "In biology, a gene is a basic unit of heredity and a sequence of nucleotides in DNA or RNA that encodes the synthesis of a gene product, either RNA or protein."https://en.wikipedia.org/wiki/Gene

In mRNA vaccines, the modification of the viral gene and its replication on a large scale can certainly be viewed as a reconstruction of genetic material. And it's made possible by a deep understanding of genes.

According to Wikipedia, gene or genome editing is "is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism". Note the distinct concept from gene therapy – as things currently stand on Wikipedia, however imperfect Wikipedia is, fundamentally. https://en.wikipedia.org/wiki/Genome_editing

> — In general I’ll note that several sentences in your answer simply make no biological sense and use made-up terms.

Maybe I've just read too much Martin-Löf and am getting overly comfortable with the abstract but I'm not worried about my ability to express my thoughts. As I'm sure you're here to build understanding, I'd like to ask you to point towards the terms you experience as made-up and the sentences that don't make sense to you. I think that is the best course of action if I am to learn anything. Otherwise I might be tempted to take it that what we are experiencing is less a lack of meaning and more a lack of comprehension.

Or to make an honest suggestion, how about we stay on topic in polite discussion and charitable interpretation?

Then in closing, I feel like I am compelled to highlight my repeated use of terms like "ambiguous" and "can be parsed". I also want to repeat that personally I wouldn't call mRNA vaccines gene therapy. We are in more general agreement too: I agree that the terms should be used as you describe. However, they can be and are used ambiguously. We are all the better for understanding this extant ambiguity, not least because the nuance and ambiguity are being abused in order to manipulate people.

Even if only from the perspective of how information on Wikipedia can be construed by the layman - such as myself.


> A modification in the frame of mind of genetic understanding is performed on a viral cell.

Let me be frank: this sentence is nonsense technobabble.

> A segment of viral genome which encodes part of the body viral is excised and modified.

No, this does not happen (even ignoring that I don’t know what “body viral” means).

> Indeed if you review my words you'll note that I explicitly address the lack of a defect.

And yet you use the term “reconstruct”. — Reconstruct what?

> The mRNA vaccines we know today can certainly be viewed as a modification and reconstruction of viral genomic material.

This sentence becomes somewhat true if we use “information” instead of “material”. But that has nothing to do with gene therapy (as you seem to acknowledge yourself later!?).

> Gene editing or genome editing is […]. Note the distinct concept from gene therapy

I hold a PhD in genomics. You do not need to explain basic molecular biology to me.

> Even if only from the perspective of how information on Wikipedia can be construed by the layman - such as myself.

Then I humbly suggest that your understanding of the subject matter as a layman is — evidently — fragmentary, and insufficient for making up your own definitions and claiming them as being equally valid as those of experts.


>> A modification in the frame of mind of genetic understanding is performed on a viral cell.

>Let me be frank: this sentence is nonsense technobabble.

>> A segment of viral genome which encodes part of the body viral is excised and modified.

>No, this does not happen (even ignoring that I don’t know what “body viral” means).

"Body viral" is an allusion to terms like "body politic" and the practice of recycling that turn of phrase in other ways. It was intended to sarcastically and self-depreciatingly refer to my misapplication of the word "cell" to virii. I make no claims on the quality of the allusion.

As I understand things: The SARS-CoV-2 genome contains a sequence that expresses a spike protein. To make the mRNA vaccines,that sequence was excised. I assume that the excision was done by genetic sequencing, so it wasn't excised from any particular virion but rather by an excision from the genome, one abstraction further up. Then the sequence is modified to change the protein that is expressed – a form that was taken from the physical construction of a virus – and modified again to allow delivery for replication in human cells.

To do something in a certain frame of mind means to see it from that perspective and to use a particular understanding to do it. I wake up in the morning and kiss my fiancee; I do that in the frame of mind of love, not from the frame of mind of facio-mandibular biomechanics. I sit down at my computer and make it do things, and I do that in the frame of mind of abstraction and symbolic manipulation. Or in the frame of mind of blowing up starbases and killing mans.

In my experience, any discussion between two entities that have an uncertain degree of mutual legibility is bound to become philosophical and fuzzy. I've also long since learned to express myself as I think and as I see. Therefore I stand by my words that a modification in the frame of mind of genetic understanding is performed on a virus.

>> Gene editing or genome editing is […]. Note the distinct concept from gene therapy

> I hold a PhD in genomics.

That's nice.

> You do not need to explain basic molecular biology to me.

Indeed I edited my comment to properly frame my message that this is the information on Wikipedia. Thanks for the quick response though! Please note that nowhere in this discussion is basic molecular biology being explained to you – at least I myself have interacted with the discussion as if it were about the ambiguity that plainly exists in the term "gene therapy" as carried in people's minds, and how that harmful ambiguity might have come about.

>> Even if only from the perspective of how information on Wikipedia can be construed by the layman - such as myself.

> Then I humbly suggest that your understanding of the subject matter as a layman is — evidently — fragmentary, and insufficient for making up your own definitions and claiming them as being equally valid as those of experts.

Nowhere have I claimed any of my words to hold as a definition, and wouldn't do so. This is a discussion in a comment section on Hacker News. Between parties with little known common ground. I'd like to repeat the term "charitable interpretation". Furthermore, I am going to do you the favor of understanding your statement that I am "making up my own definitions and claiming them as being equally valid as those of experts" as a common and minor utterance of insincere hostility rather than it being based in delusion.

Finally, it is my opinion that from the higher education I have received I derive a duty to explain and enlighten, and no rights or entitlements.




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