Transcript Level and Sequence Matching Are Key Determinants of Off-Target Effects in RNAi.

Autor: Chen J; Anhui Province Key Laboratory of Integrated Pest Management on Crops, School of Plant Protection, Anhui Agricultural University, Hefei 230036, China., Sheng CW; Anhui Province Key Laboratory of Integrated Pest Management on Crops, School of Plant Protection, Anhui Agricultural University, Hefei 230036, China., Peng Y; Institute of Entomology, Jiangxi Agricultural University, Nanchang 330045, China., Wang K; Key Laboratory of Grains and Oils Quality Control and Processing, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210046, China., Jiao Y; Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky 40546, United States., Palli SR; Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky 40546, United States., Cao H; Anhui Province Key Laboratory of Integrated Pest Management on Crops, School of Plant Protection, Anhui Agricultural University, Hefei 230036, China.
Jazyk: angličtina
Zdroj: Journal of agricultural and food chemistry [J Agric Food Chem] 2024 Jan 10; Vol. 72 (1), pp. 577-589. Date of Electronic Publication: 2023 Dec 22.
DOI: 10.1021/acs.jafc.3c07434
Abstrakt: Double-stranded RNA (dsRNA) pesticides, those based on RNA interference (RNAi) technology utilizing dsRNA, have shown potential for pest control. However, the off-target effects of dsRNA pose limitations to the widespread application of RNAi and raise concerns regarding potential side effects on other beneficial organisms. The precise impact and underlying factors of these off-target effects are still not well understood. Here, we found that the transcript level and sequence matching jointly regulate off-target effects of dsRNA. The much lower expressed target genes were knocked down to a lesser extent than genes with higher expression levels, and the critical sequence identity of off-target effects is approximately 80%. Moreover, off-target effects could be triggered by a contiguous matching sequence length exceeding 15 nt as well as nearly perfectly matching sequences with one or two base mismatches exceeding 19 nt. Increasing the dosage of dsRNA leads to more severe off-target effects. However, the length of mismatched dsRNA, the choice of different RNAi targets, and the location of target sites within the same gene do not affect the severity of off-target effects. These parameters can be used to guide the design of possibly selective sequences for RNAi, optimize the specificity and efficiency of dsRNA, and facilitate practical applications of RNAi for pest control.
Databáze: MEDLINE