Medicinal Plant tRNAs: From Hidden Sequences to Patented RNA Drugs for Cancer and Heart Disease
Transfer RNAs (tRNAs) were thought of as the cellular equivalent of backstage crew members. They were necessary for translating the genetic code into proteins, but hardly exciting enough to be stars in their own right. As research surged into DNA, proteins, and later small-molecule drugs, tRNAs sat humbly in the background, overlooked and underestimated. That picture has now changed dramatically. tRNAs and their fragments are emerging as potent therapeutic agents. They are being reimagined as real drug candidates for some of the world’s deadliest diseases, from colorectal cancer to heart disease.
Driving this shift is a growing body of pioneering studies, including important work by Professor Zhi-Hong Jiang and his team at the Macau University of Science and Technology (MUST). Their work has developed tRNAs from overlooked molecules into viable candidates for patented RNA-based drugs, bridging modern molecular science with the ancient foundations of traditional Chinese medicine.
Why tRNAs Stayed Hidden in Plain Sight
In the early years of RNA therapeutics, siRNAs captured most attention for their ability to silence disease-causing genes with high specificity. Yet they depended on prior knowledge of genetic targets, which limited their reach in complex or poorly understood diseases. Meanwhile, research into traditional Chinese medicine (TCM) focused almost entirely on its small molecules (such as ginsenosides from ginseng or paclitaxel from yew) while overlooking the vast RNA content in these plants. The assumption was that plant RNAs would be too unstable to survive digestion or enter human cells.
This neglect meant that an abundant natural library went untapped. Every medicinal plant carries tens of thousands of RNA sequences, with tRNAs and their fragments among the most plentiful. These molecules resemble siRNAs structurally and share their gene-regulating capacity, suggesting therapeutic potential that went unnoticed for decades.
From Lab to Life: The Studies Redefining tRNAs
What makes this new wave of research exciting is how it upends long-standing assumptions. Scientists once dismissed plant RNAs as irrelevant, but recent advances have proven the opposite. A significant extraction technology, known as the PARI method, has finally made it possible to extract RNA from polysaccharide-rich plants, such as ginseng, in kilogram quantities at a cost more than 90% lower than previous methods [1]. With technical hurdles removed, researchers could at last investigate tRNAs systematically.
Led by Professor Jiang, these investigations delivered profound results. A fragment from ginseng tRNA showed it could protect heart tissue from ischemia/reperfusion injury—essentially the damage caused when blood flow returns after a heart attack. In lab tests, this fragment worked over 500 times more effectively than metoprolol, a frontline medication for the heart [2]. From the Chinese yew, the same tree family that gave the world Taxol, scientists isolated a tRNA fragment capable of silencing the TRPA1 gene and stopping ovarian cancer growth [3]. Non-pathogenic strains of E. coli, long thought harmless background players in the gut, revealed tRNA fragments that kill colorectal cancer cells at nanomolar potency levels. One such fragment, EC83, proved especially powerful, offering a novel approach to designing cancer therapies [4,5]. Even Ganoderma, the “immortal mushroom” revered in traditional medicine, yielded tRNA fragments with broad anti-cancer effects, fine-tuned by subtle chemical modifications [6].
Furthermore, a tRNA fragment from Chinese yew, known as tRF-T36, was shown to target an oncogene called NUCKS1 directly. Long considered “undruggable,” NUCKS1 is overexpressed in colorectal tumors and helps drive cancer progression. By binding to NUCKS1’s genetic message, tRF-T36 shut the gene down, cutting off cancer’s fuel supply and positioning itself as a first-in-class candidate for colorectal cancer therapy [7]. Taken together, these findings transform tRNAs from overlooked molecules into a completely new drug arsenal.
Impact: From Ancient Remedies to Modern RNA Drugs
By establishing RNA as a therapeutic class within TCM, this research expands the pharmacological universe beyond small molecules and polysaccharides. The approach also redefines drug discovery: instead of starting from a known genetic target, scientists can now screen natural RNA libraries for bioactivity and trace their effects back to gene pathways—an inversion of the traditional model.
The practical outcomes are already tangible. Two RNA-based candidates, one protecting the heart from ischemic injury and another suppressing ovarian cancer, have shown strong preclinical results. On the industrial side, the work has generated five internationally granted patents, now licensed to pharmaceutical companies. These transfers represent the highest-value academic technology deals in Macau’s history.
Conclusion
The journey of tRNAs is one of science’s surprising comeback stories. Once considered as molecular “helpers,” they have re-emerged as potent medicines drawn straight from nature’s pharmacy. From ginseng roots to yew trees, from the humble E. coli to the revered Ganoderma mushroom, tRNAs and their fragments are proving that overlooked molecules can yield extraordinary results. As the first patents are filed and partnerships formed, the world may soon see RNA-based drugs inspired not by synthetic design, but by the ancient remedies of traditional medicine.
*Notes: This article provides research teasers for each reference to showcase the novelties
References
[1] T. Yan, K. Hu, F. Ren, and Z. Jiang, “LC-MS/MS Profiling of Post-Transcriptional Modifications in Ginseng tRNA Purified by a Polysaccharase-Aided Extraction Method,” Biomolecules, vol. 10, no. 4, p. 621, Apr. 2020, doi: 10.3390/biom10040621.
[2] K. Hu et al., “A tRNA-derived fragment of ginseng protects heart against ischemia/reperfusion injury via targeting the lncRNA MIAT/VEGFA pathway,” Molecular Therapy – Nucleic Acids, vol. 29, pp. 672–688, Sep. 2022, doi: 10.1016/j.omtn.2022.08.014.
[3] K.-Y. Cao et al., “A tRNA-derived fragment from Chinese yew suppresses ovarian cancer growth via targeting TRPA1,” Molecular Therapy Nucleic Acids, vol. 27, pp. 718–732, Mar. 2022, doi: 10.1016/j.omtn.2021.12.037.
[4] K.-Y. Cao, Y. Pan, T.-M. Yan, and Z.-H. Jiang, “Purification, characterization and cytotoxic activities of individual tRNAs from Escherichia coli,” International Journal of Biological Macromolecules, vol. 142, pp. 355–365, Jan. 2020, doi: 10.1016/j.ijbiomac.2019.09.106.
[5] K.-Y. Cao, Y. Pan, T.-M. Yan, P. Tao, Y. Xiao, and Z.-H. Jiang, “Antitumor Activities of tRNA-Derived Fragments and tRNA Halves from Non-pathogenic Escherichia coli Strains on Colorectal Cancer and Their Structure-Activity Relationship,” mSystems, vol. 7, no. 2, pp. e00164-22, Apr. 2022, doi: 10.1128/msystems.00164-22.
[6] F. Ren et al., “The role of post-transcriptional modification on a new tRNAIle(GAU) identified from Ganoderma lucidum in its fragments’ cytotoxicity on cancer cells,” International Journal of Biological Macromolecules, vol. 229, pp. 885–895, Feb. 2023, doi: 10.1016/j.ijbiomac.2022.12.327.
[7] K.-Y. Cao et al., “Targeting NUCKS1 with a fragment of tRNAAsn(GUU) of Chinese yew for the treatment of colorectal cancer,” Non-coding RNA Research, vol. 11, pp. 38–47, Apr. 2025, doi: 10.1016/j.ncrna.2024.11.002.
Medicinal Plant tRNAs: From Hidden Sequences to Patented RNA Drugs for Cancer and Heart Disease
Transfer RNAs (tRNAs) were thought of as the cellular equivalent of backstage crew members. They were necessary for translating the genetic code into proteins, but hardly exciting enough to be stars in their own right. As research surged into DNA, proteins, and later small-molecule drugs, tRNAs sat humbly in the background, overlooked and underestimated. That picture has now changed dramatically. tRNAs and their fragments are emerging as potent therapeutic agents. They are being reimagined as real drug candidates for some of the world’s deadliest diseases, from colorectal cancer to heart disease.
Driving this shift is a growing body of pioneering studies, including important work by Professor Zhi-Hong Jiang and his team at the Macau University of Science and Technology (MUST). Their work has developed tRNAs from overlooked molecules into viable candidates for patented RNA-based drugs, bridging modern molecular science with the ancient foundations of traditional Chinese medicine.
Why tRNAs Stayed Hidden in Plain Sight
In the early years of RNA therapeutics, siRNAs captured most attention for their ability to silence disease-causing genes with high specificity. Yet they depended on prior knowledge of genetic targets, which limited their reach in complex or poorly understood diseases. Meanwhile, research into traditional Chinese medicine (TCM) focused almost entirely on its small molecules (such as ginsenosides from ginseng or paclitaxel from yew) while overlooking the vast RNA content in these plants. The assumption was that plant RNAs would be too unstable to survive digestion or enter human cells.
This neglect meant that an abundant natural library went untapped. Every medicinal plant carries tens of thousands of RNA sequences, with tRNAs and their fragments among the most plentiful. These molecules resemble siRNAs structurally and share their gene-regulating capacity, suggesting therapeutic potential that went unnoticed for decades.
From Lab to Life: The Studies Redefining tRNAs
What makes this new wave of research exciting is how it upends long-standing assumptions. Scientists once dismissed plant RNAs as irrelevant, but recent advances have proven the opposite. A significant extraction technology, known as the PARI method, has finally made it possible to extract RNA from polysaccharide-rich plants, such as ginseng, in kilogram quantities at a cost more than 90% lower than previous methods [1]. With technical hurdles removed, researchers could at last investigate tRNAs systematically.
Led by Professor Jiang, these investigations delivered profound results. A fragment from ginseng tRNA showed it could protect heart tissue from ischemia/reperfusion injury—essentially the damage caused when blood flow returns after a heart attack. In lab tests, this fragment worked over 500 times more effectively than metoprolol, a frontline medication for the heart [2]. From the Chinese yew, the same tree family that gave the world Taxol, scientists isolated a tRNA fragment capable of silencing the TRPA1 gene and stopping ovarian cancer growth [3]. Non-pathogenic strains of E. coli, long thought harmless background players in the gut, revealed tRNA fragments that kill colorectal cancer cells at nanomolar potency levels. One such fragment, EC83, proved especially powerful, offering a novel approach to designing cancer therapies [4,5]. Even Ganoderma, the “immortal mushroom” revered in traditional medicine, yielded tRNA fragments with broad anti-cancer effects, fine-tuned by subtle chemical modifications [6].
Furthermore, a tRNA fragment from Chinese yew, known as tRF-T36, was shown to target an oncogene called NUCKS1 directly. Long considered “undruggable,” NUCKS1 is overexpressed in colorectal tumors and helps drive cancer progression. By binding to NUCKS1’s genetic message, tRF-T36 shut the gene down, cutting off cancer’s fuel supply and positioning itself as a first-in-class candidate for colorectal cancer therapy [7]. Taken together, these findings transform tRNAs from overlooked molecules into a completely new drug arsenal.
Impact: From Ancient Remedies to Modern RNA Drugs
By establishing RNA as a therapeutic class within TCM, this research expands the pharmacological universe beyond small molecules and polysaccharides. The approach also redefines drug discovery: instead of starting from a known genetic target, scientists can now screen natural RNA libraries for bioactivity and trace their effects back to gene pathways—an inversion of the traditional model.
The practical outcomes are already tangible. Two RNA-based candidates, one protecting the heart from ischemic injury and another suppressing ovarian cancer, have shown strong preclinical results. On the industrial side, the work has generated five internationally granted patents, now licensed to pharmaceutical companies. These transfers represent the highest-value academic technology deals in Macau’s history.
Conclusion
The journey of tRNAs is one of science’s surprising comeback stories. Once considered as molecular “helpers,” they have re-emerged as potent medicines drawn straight from nature’s pharmacy. From ginseng roots to yew trees, from the humble E. coli to the revered Ganoderma mushroom, tRNAs and their fragments are proving that overlooked molecules can yield extraordinary results. As the first patents are filed and partnerships formed, the world may soon see RNA-based drugs inspired not by synthetic design, but by the ancient remedies of traditional medicine.
*Notes: This article provides research teasers for each reference to showcase the novelties
References
[1] T. Yan, K. Hu, F. Ren, and Z. Jiang, “LC-MS/MS Profiling of Post-Transcriptional Modifications in Ginseng tRNA Purified by a Polysaccharase-Aided Extraction Method,” Biomolecules, vol. 10, no. 4, p. 621, Apr. 2020, doi: 10.3390/biom10040621.
[2] K. Hu et al., “A tRNA-derived fragment of ginseng protects heart against ischemia/reperfusion injury via targeting the lncRNA MIAT/VEGFA pathway,” Molecular Therapy – Nucleic Acids, vol. 29, pp. 672–688, Sep. 2022, doi: 10.1016/j.omtn.2022.08.014.
[3] K.-Y. Cao et al., “A tRNA-derived fragment from Chinese yew suppresses ovarian cancer growth via targeting TRPA1,” Molecular Therapy Nucleic Acids, vol. 27, pp. 718–732, Mar. 2022, doi: 10.1016/j.omtn.2021.12.037.
[4] K.-Y. Cao, Y. Pan, T.-M. Yan, and Z.-H. Jiang, “Purification, characterization and cytotoxic activities of individual tRNAs from Escherichia coli,” International Journal of Biological Macromolecules, vol. 142, pp. 355–365, Jan. 2020, doi: 10.1016/j.ijbiomac.2019.09.106.
[5] K.-Y. Cao, Y. Pan, T.-M. Yan, P. Tao, Y. Xiao, and Z.-H. Jiang, “Antitumor Activities of tRNA-Derived Fragments and tRNA Halves from Non-pathogenic Escherichia coli Strains on Colorectal Cancer and Their Structure-Activity Relationship,” mSystems, vol. 7, no. 2, pp. e00164-22, Apr. 2022, doi: 10.1128/msystems.00164-22.
[6] F. Ren et al., “The role of post-transcriptional modification on a new tRNAIle(GAU) identified from Ganoderma lucidum in its fragments’ cytotoxicity on cancer cells,” International Journal of Biological Macromolecules, vol. 229, pp. 885–895, Feb. 2023, doi: 10.1016/j.ijbiomac.2022.12.327.
[7] K.-Y. Cao et al., “Targeting NUCKS1 with a fragment of tRNAAsn(GUU) of Chinese yew for the treatment of colorectal cancer,” Non-coding RNA Research, vol. 11, pp. 38–47, Apr. 2025, doi: 10.1016/j.ncrna.2024.11.002.
