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A Fatal Blood Disorder Was Fixed in an Embryo Using Precision Gene Editing

They swapped just two DNA letters! ðŸ˜²

MIKE MCRAE
29 SEP 2017
 

In the wake of the first gene-edited embryos in the US being created earlier this year, Chinese researchers have employed a different technique to swap a single base in a human embryo's genome.

 

The precise edit was designed to return functionality to a gene responsible for a component of haemoglobin, which in its mutated form results in an often fatal blood condition called beta-thalassaemia.

A team of researchers from Sun Yat-sen University in Guangzhou, China, used what's called a base editor technique to change a single G back to an A in the DNA code of an embryonic cell's HBB gene.

The change might have been tiny, but in its mutated form HBB can't produce the protein beta-globin needed to build the oxygen-carrying haemoglobin for our red blood cells.

A shortage of haemoglobin means a shortage of oxygen, impeding growth and development and leading to a lifetime of blood transfusions to treat anaemia – if the embryo survives at all.

Beta-thalassaemia is usually a recessive condition, meaning both parents need to contribute a copy of the mutated gene for anaemia to develop in their child.

Correcting the mutations in this gene could help parents carry an embryo to term, or remove the trait from family lines.

About 400 different kinds of code-corruptions can affect HBB.

 

In this case, the researchers focussed on a single point-mutation that targets a base called cytosine (C) and exchanges it for one called thymine (T).

Each of these letters complements the other two kinds of base – thymine is a jigsaw-puzzle piece that matches adenine (A), while cytosine matches guanine (G).

By swapping a C for a T, the mutation should revert back to the proper 'A' code.

If this base editing technology seems unnecessarily complicated, there's a good reason for doing a genetic do-si-do – it means the strand of DNA isn't being snipped all the way through.

To test if the procedure was feasible, the team created a cell line with pieces of the gene embedded inside and then used two different base editing techniques to change the code.

Satisfied the editing could be done, they took the process to the next level and edited the gene in skin cells from a beta-thalassemia patient.

Researchers transferred the nucleus of the patient's skin cells into 30 mature oocytes – or human egg cells.

One of the techniques was then applied to the 26 cells that survived the cloning procedure, which successfully turned the G to an A in 9 of the embryos, and a G to a C (cytosine) in one.

 

None of the embryos were developed further or implanted.

Gene editing has been big news in recent years with advances in the application of a technology called CRISPR, which uses enzymes found in bacteria to chew up DNA at a specific location.

Applying this kind of corrective genetic surgery to human embryos could spell an end to a variety of inherited conditions, but so far efforts have been controversial, to say the least.

Questions have developed recently on whether or not the technology produces unwanted mutations, indicating that for all of its promise, it's still early days for this revolutionary engineering tool.

Base editing won't replace CRISPR, but could be a more delicate solution for those solitary mutations.

"We are the first to demonstrate the feasibility of curing genetic disease in human embryos by base editor system," researcher Junjiu Huang told the BBC.

Feasibility is the word here. We're nowhere near a safe operating procedure for repairing genes we consider broken in embryos.

But each careful step, coupled with healthy public debate, brings us a bit closer to an age when debilitating conditions like beta-thalassemia will be notes in a medical history book.

This research was published in Protein & Cell.

 

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