Base editing

Base editing is a genome-editing method that converts one DNA base pair into another without deliberately creating a double-strand DNA break. It uses a programmable DNA-binding system linked to an enzyme that chemically modifies a target base.

Cytosine base editor: A base editor that converts a target cytosine–guanine pair into a thymine–adenine pair. It deaminates cytosine and relies on DNA repair to establish the intended substitution.
DNA base pair: A pair of complementary nucleobases joined across the two strands of a DNA molecule. Base editors change one member of a paired site, altering the corresponding pair.
Sickle cell disease: An inherited blood disorder caused by a hemoglobin variant that makes red blood cells prone to sickling. Base editing strategies can alter hemoglobin-related DNA to raise fetal hemoglobin or address disease-causing variants.
CRISPR-Cas9: A genome-editing system that uses a guide RNA and Cas9 protein to target specific DNA sequences. Conventional Cas9 editing usually cuts both DNA strands, unlike base editing.
Off-target effects: Unintended biological changes caused by an intervention at sites or processes beyond its intended target. Base editors can alter DNA at unintended genomic sites or modify RNA, depending on the editor.
Adenine base editor: A base editor that converts a target adenine–thymine pair into a guanine–cytosine pair. It uses an engineered deaminase to turn adenine into inosine, which cells read as guanine.
Cytosine deamination: A chemical reaction that removes an amino group from cytosine, producing uracil. Cytosine editors initiate their conversion by deaminating cytosine.
Familial hypercholesterolemia: An inherited disorder in which impaired clearance of low-density lipoprotein raises blood cholesterol from early life. Researchers have tested in vivo base editing of PCSK9 as a route to lower LDL cholesterol.
Homology-directed repair: A DNA repair pathway that uses a homologous template to repair a double-strand break accurately. It can install precise changes after a programmed cut, but is less active in many non-dividing cells.
Mosaicism: The presence of genetically distinct cell populations within one organism derived from a single fertilized egg. Uneven editor delivery or activity can leave treated tissues with a mixture of edited and unedited cells.

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