Targeted knockout of a host peroxisomal peptidase confers field resistance to maize lethal necrosis
- Mark Jung
- Zhengyu Wen
- Sabrina Humbert
- Fengzhong Lu
- Alyssa DeLeon
- Lisa Marshall
- Craig Hastings
- Heather Cartwright
- Katherine Thilges
- Ning Wang
- Kassandra Breckenridge
- Emily Wu
- Larisa Ryan
- Kevin Fengler
- Kevin Simcox
- Shawn Thatcher
- Victor Llaca
- Grace Woollums
- Jeffry Sander
- Deping Xu
- Mary Beatty
- Kent Brink
- Maria Fedorova
- Mark Jones
- Erik Ohlson
- L. M. Suresh
- Yoseph Beyene
- Michael Olsen
- Veronica Ogugo
- Amos Alakonya
- Ann Murithi
- Stephen Mugo
- James Karanja
- Prasanna Boddupalli
- Kevin Pixley
- Marc Albertsen
- Todd Jones
- Robert Meeley
- Neal Gutterson
- Barbara Mazur
- Kanwarpal S. Dhugga
2026-04-30
Maize lethal necrosis (MLN) is a severe disease caused by the combined infection of maize chlorotic mottle virus (MCMV) and a potyvirus, most often sugarcane mosaic virus (SCMV). This disease seriously threatens food security across sub-Saharan Africa (SSA). We investigated a major-effect quantitative trait locus for resistance on chromosome 6, named the maize lethal necrosis susceptibility locus 1 ( qMLNS1 ), derived from the Thai line KS23-6. Fine mapping and CRISPR-Cas9 editing of the candidate genes within the narrowed 105 kb interval revealed a peroxisomal peptidase as the underlying cause of susceptibility. Confocal microscopy confirmed the localization of the MLNS1 protein within peroxisomes. Targeted knockout of the Mlns1 gene in the susceptible elite line CML536 from SSA conferred resistance comparable to KS23-6 in field trials conducted in Naivasha, Kenya. This knockout specifically blocked MCMV accumulation without affecting SCMV. The edited lines showed no yield penalty or agronomic defects under disease-free conditions. Our findings uncover a mechanistic link between a peroxisomal enzyme and viral susceptibility. They also establish a rapid, scalable gene editing strategy for incorporating MLN resistance into elite germplasm, offering a model for combating similar viral diseases in staple crops globally.