Targeted knockout of a host peroxisomal peptidase confers field resistance to maize lethal necrosis

M Mark Jung (Corteva Agriscience) Z Zhengyu Wen (International Center for Maize and Wheat Improvement) S Sabrina Humbert (Corteva Agriscience) F Fengzhong Lu (International Center for Maize and Wheat Improvement) A Alyssa DeLeon (Corteva Agriscience) L Lisa Marshall (Corteva Agriscience) C Craig Hastings (Corteva Agriscience) H Heather Cartwright (Corteva Agriscience) K Katherine Thilges (Corteva Agriscience) N Ning Wang K Kassandra Breckenridge (Corteva Agriscience) E Emily Wu L Larisa Ryan (Corteva Agriscience) K Kevin Fengler (Corteva Agriscience) K Kevin Simcox (Corteva Agriscience) S Shawn Thatcher (Corteva Agriscience) V Victor Llaca (Corteva Agriscience) G Grace Woollums (Corteva Agriscience) J Jeffry Sander (Corteva Agriscience) D Deping Xu (Corteva Agriscience) M Mary Beatty (Corteva Agriscience) K Kent Brink (Corteva Agriscience) M Maria Fedorova M Mark Jones (Corn, Soybean, and Wheat Quality Research Unit, United States Department of Agriculture-Agricultural Research Service) E Erik Ohlson (Corn, Soybean, and Wheat Quality Research Unit, United States Department of Agriculture-Agricultural Research Service) L L. M. Suresh (International Center for Maize and Wheat Improvement) Y Yoseph Beyene (International Center for Maize and Wheat Improvement) M Michael Olsen (International Center for Maize and Wheat Improvement) V Veronica Ogugo (International Center for Maize and Wheat Improvement) A Amos Alakonya (International Center for Maize and Wheat Improvement) A Ann Murithi (International Center for Maize and Wheat Improvement) S Stephen Mugo (International Center for Maize and Wheat Improvement) J James Karanja (Kenyan Agricultural and Livestock Research Organization) P Prasanna Boddupalli (International Center for Maize and Wheat Improvement) K Kevin Pixley (International Center for Maize and Wheat Improvement) M Marc Albertsen (Corteva Agriscience) T Todd Jones (Corteva Agriscience) R Robert Meeley (Corteva Agriscience) N Neal Gutterson (Corteva Agriscience) B Barbara Mazur (Corteva Agriscience) K Kanwarpal S. Dhugga (International Center for Maize and Wheat Improvement)

Abstract

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.

Article Details

Volume / Issue Vol. 123, Issue 18
Published May 05, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (41)

M

Mark Jung

Corteva Agriscience

Z

Zhengyu Wen

International Center for Maize and Wheat Improvement

S

Sabrina Humbert

Corteva Agriscience

F

Fengzhong Lu

International Center for Maize and Wheat Improvement

A

Alyssa DeLeon

Corteva Agriscience

L

Lisa Marshall

Corteva Agriscience

C

Craig Hastings

Corteva Agriscience

H

Heather Cartwright

Corteva Agriscience

K

Katherine Thilges

Corteva Agriscience

N

Ning Wang

K

Kassandra Breckenridge

Corteva Agriscience

E

Emily Wu

L

Larisa Ryan

Corteva Agriscience

K

Kevin Fengler

Corteva Agriscience

K

Kevin Simcox

Corteva Agriscience

S

Shawn Thatcher

Corteva Agriscience

V

Victor Llaca

Corteva Agriscience

G

Grace Woollums

Corteva Agriscience

J

Jeffry Sander

Corteva Agriscience

D

Deping Xu

Corteva Agriscience

M

Mary Beatty

Corteva Agriscience

K

Kent Brink

Corteva Agriscience

M

Maria Fedorova

M

Mark Jones

Corn, Soybean, and Wheat Quality Research Unit, United States Department of Agriculture-Agricultural Research Service

E

Erik Ohlson

Corn, Soybean, and Wheat Quality Research Unit, United States Department of Agriculture-Agricultural Research Service

L

L. M. Suresh

International Center for Maize and Wheat Improvement

Y

Yoseph Beyene

International Center for Maize and Wheat Improvement

M

Michael Olsen

International Center for Maize and Wheat Improvement

V

Veronica Ogugo

International Center for Maize and Wheat Improvement

A

Amos Alakonya

International Center for Maize and Wheat Improvement

A

Ann Murithi

International Center for Maize and Wheat Improvement

S

Stephen Mugo

International Center for Maize and Wheat Improvement

J

James Karanja

Kenyan Agricultural and Livestock Research Organization

P

Prasanna Boddupalli

International Center for Maize and Wheat Improvement

K

Kevin Pixley

International Center for Maize and Wheat Improvement

M

Marc Albertsen

Corteva Agriscience

T

Todd Jones

Corteva Agriscience

R

Robert Meeley

Corteva Agriscience

N

Neal Gutterson

Corteva Agriscience

B

Barbara Mazur

Corteva Agriscience

K

Kanwarpal S. Dhugga

International Center for Maize and Wheat Improvement