# Targeted Protein Degradation for Agricultural Applications: Rationale, Challenges, and Outlook

## TL;DR

Targeted protein degradation, a promising technology in medicine, could revolutionize sustainable crop protection by selectively eliminating harmful proteins in pests.

## Contribution

This paper explores the potential of targeted protein degraders as a novel, sustainable solution for agricultural crop protection.

## Key findings

- Targeted protein degraders have shown functionality in insect cells and whole organisms.
- The technology offers a potentially disruptive alternative to traditional small molecule inhibitors in agriculture.
- Regulatory and environmental challenges must be addressed for successful application in agriculture.

## Abstract

Farmers urgently
need novel technologies to ensure global food
security for the rapidly expanding population, yet crop protection
has seen little innovation in decades. Mounting regulatory pressures,
pest resistance, and environmental concerns are driving demand for
novel sustainable solutions. Beyond traditional small molecule active
ingredients, very few alternative modalities (e.g., peptides, RNAi, biopesticides) have reached the market. Meanwhile,
targeted protein degradation (TPD) has emerged as a breakthrough modality
for human therapeutics, with numerous proteolysis-targeting chimeras
(PROTACs) and molecular glues (MGs) advancing through clinical trials.
Those compounds induce potent and selective degradation of protein
targets via the ubiquitin-proteasome system (UPS). Recently, PROTACs
have been shown to function in both insect cells and in whole insect
organisms, marking a pivotal step toward their use as next-generation
crop protection solutions. In this perspective, we showcase the rationale,
key challenges, and potential breadth of applications of targeted
protein degraders for agricultural purposes. The TPD technology is
a promising and potentially disruptive alternative to traditional
small molecule inhibitors in agriculture.