Nivedita Mishra,
Rakshita Shrivastava,
Deeksha Mital,
Palak Bhatia,
- Assistant Professor, Department of Biotechnology, Center of Excellence in Plant & Microbial Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, India, Uttar Pradesh, India
- Student, B.Tech., Department of Biotechnology, Center of Excellence in Plant & Microbial Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, India, Uttar Pradesh, India
- Student, B.Tech., Department of Biotechnology, Center of Excellence in Plant & Microbial Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, India, Uttar Pradesh, India
- Student, B.Tech., Department of Biotechnology, Center of Excellence in Plant & Microbial Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, India, Uttar Pradesh, India
Abstract
Medicinal plants are natural biofactories producing secondary metabolites with significant therapeutic value, including terpenoids, alkaloids, and phenolics. Among these, artemisinin, a sesquiterpene lactone from Artemisia annua L. is the cornerstone of global antimalarial therapy along with additional anticancer, antiviral, and antimicrobial activities. However, artemisinin content in the native plants is inherently low (typically 0.01–0.8% dry weight), restricting affordable and consistent supply. Conventional approaches to increase production include classical breeding, singlegene overexpression, and RNAi-based suppression of competing pathways. These approaches have achieved only incremental improvements and are constrained by limited precision, off-target pathway effects, and regulatory challenges as they include foreign DNA introduction. CRISPR/Cas9-based genome editing has emerged as a transformative solution, enabling precise and multiplexed modification of endogenous genes governing secondary metabolic pathways. In A. annua, CRISPR strategies targeting the squalene synthase (SQS) gene which diverts the shared farnesyl diphosphate precursor toward competing sterol biosynthesis are expected to substantially increase artemisinin flux. Disruption of negative transcriptional regulators (including AaMYB15, AabHLH2/3, AabHLH5, and TrichomeLess Regulator 3) and activation of positive regulators (AaWRKY9, AaMYC3) by CRISPR provide strategies to enhance pathway gene expression. Integration of CRISPR with singlenucleus transcriptomics, comprehensive multi-omics databases (ArtemisiaDB), and AI-assisted sgRNA design platforms maximizes the precision, efficiency, and safety of editing operations. The combined effect of pathway flux redirection, negative regulator knockout, and trichome engineering is expected to achieve artemisinin yields significantly above those of current high-producing varieties. These advances hold the potential to reduce production costs, stabilize global supply, and improve access to life-saving antimalarial medicines. The principles developed in A. annua are broadly transferable to other medicinal plant systems, positioning CRISPR-based metabolic engineering as a cornerstone of next-generation plant biotechnology for sustainable pharmaceutical production.
Keywords: Artemisinin, CRISPR/Cas9, secondary metabolites, Artemisia annua, genome editing, glandular secretory trichomes
[This article belongs to Research and Reviews : A Journal of Biotechnology ]
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Research and Reviews : A Journal of Biotechnology
| Volume | 16 | |
| Issue | 02 | |
| Received | 25/06/2026 | |
| Accepted | 20/07/2026 | |
| Published | 01/08/2026 | |
| Publication Time | 37 Days |