Most people (95%+ ?) with Genetic FMO3 Malodor / TMAU1 probably have missense variants.
A new recent DNA-editing breakthrough is BASE-EDITING, where the actual variant can be replaced.
This looks ideal for correcting variants.
So far not used in humans (? some sickle cell disease sufferers got gene therapy in late 2019).
A new USA paper used base-editing in mice (given) progeria due to a missense mutation.
First results look encouraging.
Ultimately base-editing (but perhaps Crispr) will likely be (?) the cure for many genetic disorders where missense variants are the problem, including maybe 95%+ of genetic FMO3 Malodor / TMAU cases.
When ?
NIH Director Francis Collins did not expect it in his lifetime.
Now it is being used in mice.
So who knows, maybe 20 years or much sooner ?
This is a random guess.
Quotes :
In this same spirit on behalf of the several hundred kids worldwide with progeria and their families, a research collaboration, including my NIH lab, has now achieved a key technical advance to move non-heritable gene editing another step closer to the “can do” category to treat progeria. As published in the journal Nature, our team took advantage of new gene-editing tools to correct for the first time a single genetic misspelling responsible for progeria in a mouse model, with dramatically beneficial effects [1, 2]. This work also has implications for correcting similar single-base typos that cause other inherited genetic disorders. ...
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It turns out that the original CRISPR system, as powerful as it is, works better at knocking out genes than correcting them. That’s what makes some more recently developed DNA editing agents and approaches so important. One of them, which was developed by David R. Liu, Broad Institute of MIT and Harvard, Cambridge, MA, and his lab members, is key to these latest findings on progeria, reported by a team including my lab in NIH’s National Human Genome Research Institute and Jonathan Brown, Vanderbilt University Medical Center, Nashville, TN.
The relatively new gene-editing system moves beyond knock-outs to knock-ins [3,4]. Here’s how it works: Instead of cutting DNA as CRISPR does, base editors directly convert one DNA letter to another by enzymatically changing one DNA base to become a different base. The result is much like the find-and-replace function used to fix a typo in a word processor. What’s more, the gene editor does this without cutting the DNA. ...
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We are hopeful this gene editing work might eventually lead to a cure for progeria. But mice certainly aren’t humans, and there are still important steps that need to be completed before such a gene-editing treatment could be tried safely in people. In the meantime, base editors and other gene editing approaches keep getting better—with potential application to thousands of genetic diseases where we know the exact gene misspelling. As we look ahead to 2021, the dream envisioned all those years ago about fixing the tiny DNA typo responsible for progeria is now within our grasp and getting closer to landing in the “can do” category.
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