[jfarlow]

Delivery of the RNA is hard. To the right cell type, not immediately degraded, not accidentally integrated into a critical part of the genome, with a payload that is actually effective, etc.

The original gene therapies (early 2000s) were essentially RNA therapies (adenovirus). And their unethical rush and subsequent failures caused a bit of a 'gene therapy winter' [1]. We've since made enormous progress on both the ability to safely deliver genes, but also our ability to generate/design new useful genes.

[1] https://www.labiotech.eu/in-depth/gene-therapy-history/

> In 1972, a paper titled ‘Gene therapy for human genetic disease?’ was published in Science by US scientists Theodore Friedmann and Richard Roblin, who outlined the immense potential of incorporating DNA sequences into patients’ cells for treating people with genetic disorders. However, they urged caution in the development of the technology, pointing out several key bottlenecks in scientific understanding that still needed to be addressed.

[johntb86]

Wouldn't an adenovirus be delivering DNA? mRNA can't be incorporated into the genome (barring some crazy mixing due to a retrovirus) because it's RNA.

[flobosg]

mRNA is not the only type of RNA that can be delivered. Another type could be interfering RNA targeting endogenous coding or non-coding RNA molecules.

[usrusr]

"incorporating DNA sequences into patients’ cells" is a wildly more dramatic approach than temporarily tricking a number of cells into manufacturing some protein with mRNA. It's almost like the difference between getting the browser to run your page's js vs a full remote code execution vulnerability.

[armada651]

Can we please not spread the misinformation that mRNA can somehow integrate into the genome? It feeds crazy conspiracy theories around the vaccines.

[jart]

The parent was probably confusing RNA with adenovirus which IIUC does deliver DNA that integrates itself into the genome. There are dozens of COVID vaccines under development right. Many of them are in fact DNA vaccines. To date they've only been approved for vaccinating dogs of rabies. The mRNA vaccines that companies like Pfizer are making have the advantage of not permanently changing the DNA in the target cells. Even with DNA vaccine it's not the end of the world. For example, herpes simplex (cold sores) is an example of a natural virus that integrates itself in the DNA. But it's localized and it's not something that your children are going to inherit. Another interesting fact is that the Pfizer mRNA vaccine and others are delivered using lipid nanobots rather than adenovirus which I think is cool. But DNA vaccines have even potentially cooler applications since it means the medical field might for once be able to offer cures to illnesses, rather than charging you for a pill every day.

[postalrat]

How can you say we made enormous progress when it appears this is still an untested therapy.

[jfarlow]

The number of [nucleic-acid-delivered] gene therapies in Phase II & Phase III trials right now is huge - because of this progress in delivery [of nucleic acids]. Gene therapies for the eye, for hemophilia, for sickle cell, many many cancer therapies all rely on the ability to 'deliver' nucleic acid payloads to cells. Of those, only 3 or 4 have been approved - and all in the past 2 years, but there are a huge number that are behind that tip of the iceberg - quite precisely because it's relatively straightforward to do 'same thing but with a different sequence' once the first one works.