CRISPR gallops ahead (article contains a warning for xenophobes)

Warning: this article may make uncomfortable reading for xenophobes everywhere)

Progress in CRISPR-Cas-9 (Clustered Regularly Interspaced Short Palindromic Repeats)[1] and the associated enzyme is getting faster and faster. We started reporting on this truly innovative technique in 2020 and regular readers will recall updates ever since. Only four years ago it still felt a bit theoretical. But now radical applications are coming thick and fast Read this from Nature Briefing CRISPR horses spark debate reporting on the rather recondite world of polo pony breeding

the horses pictured above{*} are the first of their species to have been created with the help of the CRISPR–Cas9 gene-editing technique. They are clones of the prize-winning steed Polo Pureza, with a tweak to myostatin — a gene involved in regulating muscle development — that is designed to quicken their pace. Critics say that genetic manipulation has no place among polo’s traditional breeding practices — it has already been banned by some of the sport’s governing bodies. But a zoo of CRISPR-edited animals, from cows to sheep, is gaining acceptance in agriculture.Nature | 5 min read

{*} sorry LSS readers-we can’t show this-ed

In one sense there’s nothing new here. Humans have been modifying the genetics of plant and animal species since the dawn of the Neolithic. CRISPR and other base editing techniques have simply speeded the whole process up by making specific, designed changes and crucial nodes in the subject organism’s development. There is every reason to suppose that any number of new modifications to animals(and crop plants such as wheat) will be developed in the next few years. Some may even enable us the preserve the integrity of food supplies despite the ravages of things like plastics pollution and global warming. Also, as we have also reported here, gene editing is beginning to show real applications in medical fields such as sickle cell disease and certain cancer therapies. All of which leads us to an intriguing thought.

If ponies may be so easily modified, why not humans? One could start small by just modifying athletes and other small groups. Yet eventually the techniques could become ubiquitous in our species. Hang on-our species? Because the genetic differences between beings consisting entirely of CRISPR modified genes and the rest of us would then be far, far greater than those currently existing between our different races and ethnic groups. Are xenophobes everywhere already wasting their own time?

[1]https://www.yourgenome.org/theme/what-is-crispr-cas9/

#CRISPR Cas 9 #base pair #medicine #biotechnology #sickle cell #agriculture #stock breeding

We said Base Pair editing would outshine CRISPR. This breakthrough proves we were wrong. Or not

When is CRISPR- Cas-9 Base Pair Editing, and when is Base Pair editing CRISPR Cas-9?. Readers of this blog may be forgiven for thinking Base Pair Editing was the exciting new kid in town that was going to make CRISPR look like VHS tapes ( what they?ed) But according to reports of a recent breakthrough in medicine, they are, sort of, one and the same thing.

Perhaps we had better start with the breakthrough. Doctors in Pennsylvania in the USA have used gene editing techniques to treat a poor little boy whose liver lacked the necessary enzyme system to process ammonia. Our reports come firstly from Ian Sample of the Guardian and the New England Journal of medicine via hyperlink) , where Base Pair is very much to the fore While Nature Briefing has the following take , again with the hyperlink to the NEJM, Baby Boy Receives CRISPR for One Therapy

A baby boy with a devastating genetic disease is thriving after becoming the first known person to receive a bespoke, CRISPR therapy-for-one. KJ Muldoon, now almost 10 months old, received three doses of a gene-editing treatment designed to repair his specific disease-causing mutation, which impaired his body’s ability to process protein. While Muldoon appears healthy, it is too soon to use the word “cure”, says paediatrician Rebecca Ahrens-Nicklas. “This is still really early days.”Nature | 5 min read
Reference: New England Journal of Medicine paper

From all of which we have obtain the following Learning Points for your Edification , gentle reader:

1 It matters less what you call it, and more that it works-the kid’s OK now!

2 Maybe Base Pair Editing is a subset of CRISPR the way that Hammersmith is a region of London. OK, it’s Hammersmith. But it’s London too. What’s the big deal?

3 It would be interesting to learn if other big cities like New York or Madrid for examples, contain smaller areas with funny names. But we will leave that to another day.

4 If you educate people, teach them critical thinking skills and give them some money to buy test tubes with, things like this can happen

5 If you keep people working long hours for little money, educate them to a minimum and give them things like Fox News to watch, societal outcomes may be very different

[1]https://www.theguardian.com/science/2025/may/15/us-doctors-rewrite-dna-of-infant-with-severe-genetic-disorder-in-medical-first?CMP=Share_iOSApp_Other

also: see LSS 23 7 2022 and follow ups

#gene therapies #base pair editing #CRISPR Cas-9 #medicine #health

Round Up: New Brains for old, Fungal resistance, do we need growth?

Could CRISPR Cas-9 Rebuild your brain? As the brain ages, cells and circuits die off. Hence the unprecedented rise of neurodegenerative diseases in our ageing populations. Hope that this could one day be treated comes from several sources. None more so than this new development in CRISPR Cas 9 gene editing, a much touted favourite on these pages, we admit. Here’s the inimitable Nature Briefings:

Reducing the activity of one particular gene in ageing mice rejuvenates brain stem cells, allowing them to proliferate and provide a supply of fresh neurons. Researchers used CRISPR-Cas9 genome editing to systematically disrupt 23,000 genes and test the effects on neural stem cells. Messing with one such gene, Slc2a4, reduced stem cells’ glucose intake and increased their power to proliferate in old animals, but didn’t affect the cells in young mice. The results provide crucial information for the design of cell therapies that might one day treat neurodegenerative conditions, says neuroscientist Saul Villeda.Nature | 5 min read
Reference: Nature paper

Fungal resistance: a growing problem. Regular readers of these illustrious pages could be forgiven for thinking we spend too much time on antibacterial resistance among bacteria, and not enough on fungi. We hope this very prescient article from The Conversation may go some way to correcting this imbalance

https://theconversation.com/antifungal-resistance-is-not-getting-nearly-as-much-attention-as-antibiotic-resistance-yet-the-risks-to-global-health-are-just-as-serious-239677?utm

Good Growth/Bad Growth The difference in utility between having a small family car, such as a Vauxhall Corsa, and no car at all, is very great indeed. The differences between having that same Corsa and a Rolls Royce are, we humbly submit, rather marginal. Unless you count the awe-inspiring status statement which the latter brings. Growth is good for raising people out of poverty. Yet for centuries it has been based on the production and consumption of status goods rather than useful ones. The complexities of this issue are so fiendish, that we have never known where to begin to understand it. But Larry Elliott of the Guardian makes a brave first try at untying the Gordian knot:

https://www.theguardian.com/business/2024/oct/20/degrowth-image-problem-solve-planet-climate

#veblen #growth #status #antimicrobial resistance #CRISPR Cas 9 #alzheimers #medicine #health

Goodbye CRISPR and epigenetic medicine. Two genuinely exciting developments in one day

Far in the future when the current crop of elections in France, the UK, Iran and the USA are lost in the dusty pages of history books, people will remember this sunny weekend . For it was when Nature Briefings published not one but two stories (count ’em!) about learning and technologies which will still be shaping the lives of those yet unborn. And you read about them here, gentle reader!

Epigenetic Advance From one time Cinderella to starring role, the science of Epigenetics(all that stuff hanging around DNA but isn’t your honest to goodness genome)[1] has started to come of age. Proof of this lies in the fact that it’s starting to become the basis of real cures, in this case for Prion-based diseases “Epigenome Editor” blocks bad proteins

A molecular-editing tool that’s small enough to be delivered to the brain shows promise for warding off prion diseases, a rare but deadly group of neurodegenerative disorders. The system — known as coupled histone tail for autoinhibition release of methyltransferase (CHARM) — changes the ‘epigenome’, a collection of chemical tags that are attached to DNA and that affect gene activity. In mice, CHARM silenced the gene that produces the disease-causing proteins in most neurons across the brain without altering the gene sequence. This system is the first step towards developing a safe and effective ‘one and done’ treatment for reducing the levels of harmful proteins that cause prion disease, says bioengineer Madelynn Whittaker.Nature | 5 min read
Reference: Science paper

Goodbye CRISPR, welcome Bridge RNA Remember how this blog used to wax lyrical about CRISPR back in the ancient days of 2022? Well, there’s a new kid on the block “Jumping Gene” enzyme edits genomes

A technique that harnesses ‘jumping genes’ — mobile genetic sequences naturally found in bacteria that can cut, copy and paste themselves into genomes — could hold the key to redesigning DNA at will. Guided by an RNA molecule called a ‘bridge’ RNA or ‘seekRNA’, the system has been shown to edit genes in a bacterium and in test-tube reactions, but it is still unclear whether it can be adapted to work in human cells. If it can, it could be revolutionary, owing to its small size and its ability to make genetic changes that are thousands of bases long — much larger than is practical with the CRISPR — without breaking DNA.Nature | 6 min read
Reference: Nature paper 1Nature paper 2 & Nature Communications paper

You’re a funny old species, aren’t you? When you use your inherent qualities of curiosity and intelligence you can achieve things like this. The rest of the time you divide yourselves into imaginary groups and spread destruction, holding yourselves back by centuries from a better life. Will someone pray tell us why you do it?

[1]https://www.wob.com/en-gb/books/nessa-carey/epigenetics-revolution/9781848312920?msclkid=f5800b66adbb110d62696d196c3d84a0&utm_source=bing&utm_m

#medicine #epigenetics #genetics #prions #gene editing

Two amazing stories from genetics that woke us up this morning

One of our great pleasures in life is to stand amazed when someone does something amazingly clever. Especially when you get that feeling that what they did was there, waiting to be done, all along. Which is why we bring you two such stories, all gift wrapped up by the admirable Nature Briefings and BBC, for you to click on at your delight.

A Cure for HIV? Anyone who lived through the 1980s will recall the terrible ravages of the AIDS pandemic, caused of course by the HIV virus. Even if you were lucky enough to be in a low-risk group, we all knew someone or a local community organisation who suffered the ravages. Sad. Sad. Sad. Now that old friend of LSS, CRISPR gene editing may actually offer some hope towards the final elimination of the virus from our genomes. It’s early days yet, as both Michelle Roberts of the BBC and the researchers themselves say. Proof of concept and all that. Good, it’s better to be cautious. But if they can “snip” the HIV virus out of your cells, what else might not be achieved?[1]

Ghost DNA made us brainy Talking of embedded DNA, many a 1980s conversation concerned all that mysterious DNA lying around our genomes that didn’t seem to do anything (no, it was mainly about EastEnders-ed) Was it some of it ancient embedded viruses that attacked our ancestors long ago, in some forgotten Permian Pandemic? Well, get this from Nature Briefings, Virus Helped Brain Evolution

Remnants of an ancient viral infection are essential for producing myelin, a protein that insulates nerve fibres, in most vertebrates. Certain viruses insert DNA into the genetic material of the cells they invade. Sometimes, these insertions become permanent and even aid evolutionary processes. Myelin helps nerves to send electrical signals faster, grow longer and thinner so they can be packed in more efficiently. “As a result of myelin, brains became more complex and vertebrates became more diverse,” says stem-cell biologist and study co-author Robin Franklin.Science News | 6 min read
Reference: Cell paper

The implications are rather profound. The idea of the single autonomous gene line, the pure selfish individual at the core of your biological identity is rather compromised, isn’t it? What if the genetic “you” isn’t just “you,” but is you+some (rather random )free riders, who may or may not be helpful? That Natural Selection is acting on several of you at once. and may force you to cooperate? What price The Selfish Gene now?

[1]https://www.bbc.co.uk/news/health-68609297

#genetics #dna #rna #hiv #aids #myelin #evolution #CRISPR #medicine