World-first use of base-edited cells to treat 'incurable' leukaemia

Everyday Science Science & Technology

16-Dec-22

Context: An incurable cancer was cleared inside the body of a teenage girl with the use of a revolutionary gene therapy after all other treatments failed to cure 13-year-old Alyssa's leukaemia.

Key Points

A 13-year-old girl Alyssia in the UK who has T-cell acute lymphoblastic leukaemia received experimental gene therapy that relied on a new technique called ‘base editing.’ She now has no detectable cancer cells.
In T-cell acute lymphoblastic leukaemia, or T-ALL, the T-cells, which are a class of white blood cells, equipped to hunt and neutralise threats to the body, turn against the body and end up destroying healthy cells that normally help with immunity.
The disease is rapid and progressive and is usually treated by chemotherapy and radiation therapy.
The objective of the therapy in the case of T-cell leukaemia was to fix her immune system in a way that it stops making cancerous T-cells.

What is ‘base editing?’

A person’s genetic code is several permutations of four bases: Adenine (A), Guanine (G), cytosine (C) and thymine (T).
Sequences of these bases spell out genes that are instructions to produce the wide array of proteins necessary for the body’s functions.
In Alyssia’s case, her T-cells had become cancerous because of a mis-arrangement in the sequence of bases.
Correcting this mis-arrangement could mean a healthier immune system. The most popular approach to allow genes to be altered and errors fixed has been the CRISPR-cas9 system.
The CRISPR-cas9 system is believed to be the fast, most versatile system to effect such gene editing.
The CRISPR-cas 9 system consists of an enzyme that acts like molecular scissors. It can be made to cut a piece of DNA at a precise location and a guide RNA can be used to insert a changed genetic code at the sites of the incision.
David Liu of the Broad Institute, Massachusetts has improvised on the CRISPR-cas9 system to be able to directly change certain bases: thus, a C can be changed into a G and T into an A.
Base editing is reportedly more effective at treating blood disorders which are caused by single point mutations, or when a change in a single base pair can cause terminal disease.