[DIYbio] Re: Are DNA vaccines the future?

Is the "free DNA" really free? I thought I read it's enclosed into lipid particles/vesicles very soon, and if this is defect this might cause problems? 

There are lots of nucleases in the blood so any free DNA sould be degraded pretty soon  https://www.ncbi.nlm.nih.gov/pubmed/25746148 "The endogenous nuclease activity was 14.9-fold higher in serum compared to EDTA-plasma. The DNAse I treatment did not alter the ccffDNA yields in EDTA-plasma, but completely degraded it in serum."

On Wednesday, June 7, 2017 at 3:45:26 PM UTC+2, ukitel wrote:
I don't think it's not so straightforward, with the inject dsDNA->anti-dsDNA antibodies idea
There is free DNA in the blood all the time, coming from your own dead cells, which is indeed now used for liquid biopsy and sequencing.
This must mean that developing the mere presence of free DNA does not lead automatically to anti-dsDNA antibodies.

It would probably depend (among many other things) on the concentration. And for a DNA vaccine I imagine that such concentration is quite low. Indeed, you would rely on the subsequent expression of protein at high levels from that DNA.

I would be more "worried" about the immune cells mounting a response against your own cells (transfected with the DNA) and developing an auto-immune disease in the process. The survival of plasmacells depends on the inflammatory environment and their stimulation with the antigen, this leads to some tolerance for cross-reactive and auto-antibodies during infections.
In the case of DNA vaccine the non-self antigen is being produced and presented (on MHC-I complexes) by self-cells, so I can imagine that there will be a certain degree of cross-fire.
Once the transfected cells are cleared out, the cross-reactive antibodies should also clear out, but there might be some exceptions to this.

On Monday, 5 June 2017 04:35:29 UTC+2, Andreas Stuermer wrote:
Hi everyone!

I came across DNA vaccination studies and this quite confuses me. There are no DNA vaccines approved as of yet (for humans).

A) If you inject DNA, isn't there a chance that this induces anti-dsDNA antibodies? Most studies say no, some say it may be possible (if you are a lupus prone mouse).

B) This might be explained by this - before immune cells are released into action, they have to mature in the thymus. There the body disposes of autoreactive cells. But there won't be much DNA floating outside so it may not clear all anti-dsDNA reactive antibodies?

C) Injecting complexed DNA is safer because it is being shielded from immune cells?

D) vaccines have adjuvants, one of them is synthetic CpG oligonucleotide. If one was afriad of getting lupus from injecting anti-dsDNA antibodies, one would have to avoid vaccines in general?

E) One study for malaria DNA vaccine tested for dsDNA antibodies and just one guy tested positive. But then they retested his old blood sample and he help being positive even before the vaccine. Also HIV DNA vaccine didn't show anti dsDNA antibodies.

Would love to hear your thoughts!

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