Spray-Induced Gene Silencing Technology: from Rational Design to Industrialization

A research team led by Prof. ZHANG Tao from the Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences (XIEG), in collaboration with the Institute of Germplasm Resources and Biotechnology, Tianjin Academy of Agricultural Sciences, has recently published a systematic reference framework for advancing Spray-Induced Gene Silencing (SIGS) from proof-of-concept toward industrialization. The study was published in Communications Biology on July 14, 2026.

Global agricultural production faces increasingly severe threats from pests and pathogens, while the ecological risks of chemical pesticides continue to mount. In this context, SIGS offers a compelling alternative: it controls these threats simply by external spraying of Double-stranded RNA (dsRNA), completely bypassing the transgenic process. This approach has shown tremendous potential as a substitute for chemical pesticides.

However, the technology still faces several critical bottlenecks including the lack of a systematic framework for rational dsRNA design, insufficient large-scale production capacity, and low delivery efficiency, which constrain its critical transition from the laboratory to field applications.

To address these challenges, the research team conducted a comprehensive review across three dimensions: rational dsRNA design, large-scale production, and nanocarrier-mediated delivery.

On design, by adopting an integrated perspective spanning dsRNA design, production, and delivery, this review highlights that rational dsRNA design requires integrated consideration of five key factors. Multi-target strategies can effectively enhance silencing efficiency while reducing off-target risks. Target site accessibility exerts a greater impact on silencing efficacy than GC content, thus mRNA regions with loose secondary structure should be prioritized as target sites.

The optimal molecular length varies by species (commonly 150-550). Loop-end-enhanced dsRNA (ledRNA) can improve dsRNA stability in the insect gut environment. Additionally, the Dicer-like (DCL) processing preferences of different species require targeted matching.

On production, microbial fermentation has already reduced costs to $2-5/g, while cell-free platforms represented by Calantha®—the first EPA-approved dsRNA-based pesticide product—have achieved costs as low as $0.5-1/g. Furthermore, vector optimization strategies including high-copy plasmids, convergent dual promoters, and non-toxic induction systems, has significantly enhanced dsRNA yields.

On delivery, layered double hydroxide (LDH) nanosheets provide sustained-release protection exceeding 20 days, while carriers such as chitosan and star-shaped polycations each offer distinct advantages in overcoming environmental stability and cell-penetration barriers.

The review also systematically compares differences among delivery carriers in terms of protection efficacy, environmental stability, and biocompatibility, reflecting the current lack of unified evaluation standards in SIGS technological pathway selection.

The research team stresses that the requirements for dsRNA length, sequence, and delivery methods vary significantly across different crop systems and target organisms, suggesting that future research should move toward a more refined technology-matching framework.

Read the full article: https://doi.org/10.1038/s42003-026-10663-5

Key factors affecting dsRNA/siRNA design efficacy. (Image by XIEG)

Contact

ZHU Guoning

Xinjiang Institute of Ecology and Geography

E-mail: zhugn@ms.xjb.ac.cn

Web: http://english.egi.cas.cn