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Gene Therapy for Covid-19 (KLF2)

marcjf

Senior Member
Messages
127
Interesting paper coming out of China

The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction
https://www.nature.com/articles/s41392-021-00690-5

In short, there is a gene called Kruppel-like factor 2 (KLF2), which is vital for maintaining vascular homeostasis. Its expression was found to be reduced in Covid-19 infected individuals, and monocyte adhesion to the endothelial walls is increased. They show that by up-regulating this gene, the monocyte adhesion is decreased.

I am mostly interested in the ways that they found to up-regulate the gene in cultured endothelial cells. Here is a visual of the results:

41392_2021_690_Fig6_HTML.png


First, there is the pharmacological route. They found that Atorvastatin can up-regulate this gene. They suggest some other compounds that can have the same effect.

Now for the more adventurous route, we have gene therapy. They used adenovirus expressing Human KLF2, and also obtained same results. How close are we to have this available though? We barely have any large scale trials. Is it because there is little incentive from pharma companies?
I understand these can be more dangerous than pharmacological alternatives, but that is why trials exist.

For those more interested in gene therapy with KLF2 upregulation, there are more studies:
* Pulmonary hypertension: https://www.nature.com/articles/s41467-020-14966-x
* Atherosclerosis: https://www.nature.com/articles/s41598-018-20885-1
 

SWAlexander

Senior Member
Messages
1,898
Thanks,
Very interesting and comparable especially "encompassing multiple aspects of endothelial dysfunction including oxidative stress, mitochondrial dysfunction, endothelial cell death, endothelial-to-mesenchymal transition (EndoMT), inflammation, glycocalyx disruption, and altered cell metabolism"
1634440424701.png
 

marcjf

Senior Member
Messages
127
Thanks,
Very interesting and comparable especially "encompassing multiple aspects of endothelial dysfunction including oxidative stress, mitochondrial dysfunction, endothelial cell death, endothelial-to-mesenchymal transition (EndoMT), inflammation, glycocalyx disruption, and altered cell metabolism"
View attachment 45135

Just went to check mine as well. I do not have those SNPs in my 23andme data, although I have a much older version of the test.
It would be nice though if we could easily test these gene expressions. Our genetic mutations unfortunately will not explain everything. Infections can easily change them.
 

SWAlexander

Senior Member
Messages
1,898
"It would be nice though if we could easily test these gene expressions."
You are right. I had my first test in 2009 and now another in Jan. 2021. Now, I compare and see some changes. Some genes became activated (expressions) over the years.
Altogether it would be easier and faster to find a diagnosis when DNA is (as a guideline) available. My thinking is - if you don't have certain gene markers or mutations, you can't have this or that illness.