Tiny tools for the smallest of tasks, editing genes

YOU CAN LISTEN TO THIS BLOG AS AN AUDIOCAST ON SPOTIFY

Developing new tools to edit genes

Having the right tools to do a job is important. Try using a large screwdriver to tighten the screws on your glasses and you quickly appreciate that it’s not just the type of tool that’s important, it’s also the size. The same theory applies to gene editing. And now researchers at Stanford have developed a tool that can take on even the tiniest of jobs.

The tool involves the use of CRISPR. You may well have heard about CRISPR. The magazine New Scientist described it this way: “CRISPR is a technology that can be used to edit genes and, as such, will likely change the world.” For example, CIRM is funding research using CRISPR to help children born with severe combined immunodeficiency, a rare, fatal immune disorder.  

There’s just one problem. Right now, CRISPR is usually twinned with a protein called Cas9. Together they are used to remove unwanted genes and insert a corrected copy of the bad gene. However, that CRISPR-Cas9 combination is often too big to fit into all our cells. That may seem hard to understand for folks like me with a limited science background, but trust the scientists, they aren’t making this stuff up.

To address that problem, Dr. Stanley Qi and his team at Stanford created an even smaller version, one they call CasMINI, to enable them to go where Cas9 can’t go. In an article on Fierce Biotech, Dr. Qi said this mini version has some big benefits: “If people sometimes think of Cas9 as molecular scissors, here we created a Swiss knife containing multiple functions. It is not a big one, but a miniature one that is highly portable for easy use.”

How much smaller is the miniature version compared to the standard Cas9? About half the size, 529 amino acids, compared to Cas9’s 1,368 amino acids.”

The team conclude their study in the journal Molecular Cell saying this could have widespread implications for the field: “This provides a new method to engineer compact and efficient CRISPR-Cas effectors that can be useful for broad genome engineering applications, including gene regulation, gene editing, base editing, epigenome editing, and chromatin imaging.”

Listen up! Stem cell scientists craft new ears using children’s own cells

Imagine growing up without an ear, or with one that was stunted and deformed. It would likely have an impact on almost every part of your life, not just your hearing. But now scientists in China say they have found a way to help give children born with this condition a new ear, one that is grown using their own cells.

Microtia is a rare condition where children are born with a deformed or underdeveloped outer ear. This is what it can look like.

Microtia ear

In an interview in New Scientist, Dr. Tessa Hadlock, at Massachusetts Eye and Ear Infirmary in Boston, said:

“Children with the condition often feel self-conscious and are picked on, and are unable to wear glasses.”

In the past repairing it required several cosmetic surgeries that had to be repeated as the child grew. But now Chinese scientists say they have helped five children born with microtia grown their own ears.

In the study, published in the journal EBioMedicine, the researchers explained how they used a CT scan of the child’s normal ear to create a 3D mold, using biodegradable material. They took cartilage cells from the child’s ear, grew them in the lab, and then used them to fill in tiny holes in the ear mold. Over the course of 12 weeks the cells continued to multiply and grow and slowly replaced the biodegradable material in the mold.

While the new “ear” was being prepared in the lab, the scientists used a mechanical device to slowly expand the skin on the child’s affected ear. After 12 weeks there was enough expanded skin for the scientists to take the engineered ear, surgically implant it on the child’s head, and cover it with skin.

Over the course of the next two and a half years the engineered ear took on a more and more “natural” appearance. The children did undergo minor surgeries, to remove scar tissue, but other than that the engineered ear shows no signs of complications or of being rejected.

Here is a photo montage showing the pre and post-surgical pictures of a six-year old girl, the first person treated in the study.

Microtia

Other scientists, in the US and UK, are already working on using stem cells taken from the patient’s fat tissue, that are then re-engineered to become ear cells.

Surgeons, like Dr. Hadlock, say this study proves the concept is sound and can make a dramatic difference in the lives of children.

“It’s a very exciting approach. They’ve shown that it is possible to get close to restoring the ear structure.”