The American chestnut (Castanea dentata) is a large, fast-growing deciduous tree of the beech family native to eastern North America. As is true of all species in the genus Castanea, the American chestnut produces burred fruit with edible nuts. The American chestnut was once common in the Appalachian Mountain range and was a dominant species in the oak-chestnut forest region of its central and southern range.

During the early to mid-20th century, American chestnut trees were devastated by chestnut blight, a fungal disease that came from Japanese chestnut trees that were introduced into North America from Japan. It is estimated that the blight killed between three and four billion American chestnut trees in the first half of the 20th century, beginning in 1904. Four mature American chestnuts exist within its former range, although many stumps and root systems continue to send up saplings. Most of these saplings get infected by chestnut blight, which girdles and kills them before they attain maturity. There are hundreds of large (2 to 5 ft (0.6 to 1.5 m) in diameter) American chestnuts outside its historical range, some in areas where less virulent strains of the pathogen are more common, such as the 600 to 800 large trees in Northern Michigan. The species is listed as endangered in Canada under the Species at Risk Act. American chestnuts are also susceptible to ink disease, particularly in the southern part of its native range; this likely contributed to the devastation of the species.

Several groups are attempting to create blight-resistant American chestnuts. Scientists at the SUNY College of Environmental Science and Forestry created the Darling 58 cultivar by inserting the oxalate oxidase gene from wheat into the genome of an American chestnut. When expressed in the vascular cambium of the Darling 58 cultivar, the oxalate oxidase enzyme degrades the oxalic acid produced by the chestnut blight, reducing damage to the vascular cambium and resisting girdling of the trunk. As of 2021, the researchers who developed this cultivar are working toward applying for government permission to make these trees available to the public. If approved, these chestnut trees would be the first genetically modified forest trees released into the wild in the United States. Alternate approaches to developing a blight-resistant cultivar include cross-breeding among partially blight-resistant American chestnuts or crossbreeding with the moderately blight-resistant Chinese chestnut, then backcrossing with the American chestnut, with the goal of retaining most of its genes.

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