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Kiran Musunuru Profile picture
Kiran Musunuru
@kiranmusunuru
Cardiologist, geneticist, and gene editor. Author of #TheCRISPRGeneration and #GenomeEditingAPracticalGuide
Nov 2, 2023 • 28 tweets • 12 min read
When I started working on #CRISPR to fight heart disease >10 years ago, I never imagined it might lead to cures for rare inborn errors of metabolism.

Here’s how it’s happening!

Presented/published today #ASHG23 #ASHG2023 @GeneticsSociety plenary + @AJHGNews + @HGGAdvances

🧵
Image @GeneticsSociety @AJHGNews @HGGAdvances 2/

To recap: we used lipid nanoparticles (LNPs) to deliver an adenine base editor mRNA and a guide RNA inactivating PCSK9 into the livers of monkeys.

This treatment resulted in durable reduction of blood LDL cholesterol by 60+%.



nature.com/articles/s4158…

Image
Jun 26, 2021 • 11 tweets • 6 min read
A milestone in modern medicine: 1st therapeutic in vivo gene editing in human patients!

From Julian Gillmore, @intelliatweets & colleagues out today @NEJM:

nejm.org/doi/full/10.10…

Here’s an overview of a new potential treatment for transthyretin (ATTR) amyloidosis.

(thread) 2/
Transthyretin (TTR) is expressed in liver, is secreted into blood, and functions as vitamin/hormone transporter.

ATTR amyloidosis is caused by abnormal aggregates of destabilized TTR monomers (normally forms tetramers)—either mutant or wild-type—damaging nerves and/or heart.
Jun 27, 2020 • 22 tweets • 15 min read
How to use #CRISPR gene editing to fight heart disease, the #1 killer worldwide:

A thread 10+ years in the making.

This one starts in 2009 when I was a postdoc in @skathire lab @MassGeneralNews/@broadinstitute studying ❤ risk factors like cholesterol & triglycerides.

(thread) 2/
Inspired by work from Boileau/Seidah/Breslow/Horton/Hobbs/Cohen/et al.:

1. Activating PCSK9 mutations = ⬆️LDL cholesterol

2. Inactivating mutations = ⬇️LDL & ⬇️heart disease

3. People with no PCSK9 = ⬇️⬇️LDL & *healthy*!

We asked: are there more PCSK9’s to be discovered?
Nov 26, 2019 • 17 tweets • 8 min read
Lulu and Nana, humanity’s first gene-edited babies, both have some CRISPR edits in the CCR5 gene, as He Jiankui (JK) attempted. His goal was to confer HIV resistance.

Unfortunately, the editing turned out quite badly, as shown by *his own data* in *his own manuscript*. (thread) 2/
Here’s the first piece of evidence.

This is a Sanger sequencing chromatogram of a PCR amplicon of the CCR5 target site, using DNA from cells extracted from Lulu’s embryo prior to pregnancy.

In the manuscript, JK claims there’s a wild-type allele and a 15bp deletion allele.
Nov 25, 2019 • 12 tweets • 10 min read
Today is the 1-year anniversary of @antonioregalado breaking the news about Chinese scientist He Jiankui (JK) using gene-edited human embryos to establish pregnancies.

It’s time to break the silence. (thread)

technologyreview.com/s/612458/exclu… 2/
1 year and 1 week ago, I learned that twin girls called Lulu and Nana had been born—humanity’s first gene-edited babies.

At that time, @MMarchioneAP asked me and a few other experts to assess a manuscript written by JK about the twins. I read it, and I was horrified.