- Person
- Aaron Klug
- Lived
- 1926–2018
- Field
- Structural biology
- From
- Lithuanian-born British
The story
Aaron Klug was born in 1926 to Jewish parents in Želva, Lithuania, grew up in Durban, South Africa, and spent most of his career at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. He was already famous for inventing ways to see viruses and chromosomes in three dimensions when, in 1985, his group made a discovery about how genes are switched on.
Studying a protein that binds DNA to activate a gene, Klug and his colleagues found that it was built from a series of small, repeating folds, each held together by a zinc atom. Each fold grips the DNA like a finger, reading a run of three or four DNA letters. They called them zinc fingers. Klug realized that because the fingers are modular, they could in principle be redesigned and strung together to recognize almost any chosen stretch of DNA. In 1994 his team published a zinc finger protein engineered to bind a specific DNA site.
The idea became a technology. A company spun out of Klug’s laboratory, Gendaq, was founded in 1999 and acquired in 2001 by Sangamo, an American biotechnology firm, and Klug served on Sangamo’s scientific advisory board. By attaching DNA-cutting enzymes to designed zinc fingers, researchers created zinc finger nucleases, among the first tools able to edit specific genes in living cells. They have been used in research animals, crop plants and human cells. In a clinical trial that began in 2010, they were used to disable the CCR5 gene, which HIV uses to enter immune cells, in patients’ own white blood cells.
In November 2017 a patient in California with Hunter syndrome, a severe inherited disease, was treated with an engineered zinc finger nuclease designed to insert a working copy of the faulty gene into the patient’s liver cells, the first attempt to edit a gene inside a human body. Newer tools such as CRISPR have since joined zinc fingers, but Klug’s discovery showed that precise, targeted changes to human genes were achievable.
Why it matters
Klug’s zinc fingers became the first engineered gene-editing tools, opening the path to treatments that correct faulty genes in patients.
About Aaron Klug
Lithuanian-born, South African-raised biophysicist who invented ways to see viruses and chromosomes in 3D and discovered zinc fingers, later used in the first gene-editing treatments. Nobel 1982.
Sources
- Zinc finger proteins discovered by MRC-funded research used in first gene-editing trial Cambridge Network (Medical Research Council)
- Aaron Klug (1926–2018) MRC Laboratory of Molecular Biology
- Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Subjects ClinicalTrials.gov
- Aaron Klug, Biographical NobelPrize.org
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.