Epigenetics and a new era of biological weapons
https://doi.org/10.35825/2587-5728-2025-9-4-305-321
Abstract
Highlights
- The research of epigenetic inheritance mechanisms opens up possibilities for creating new types of biological damaging agents and changing the targets and methods of biological warfare.
- The use of epigenetic mechanisms for in vivo gene expression manipulation requires the development of strict international regulatory protocols, biosecurity systems, and broad public discussion about the ethical boundaries of scientific intervention.
Relevance. Driven by the explosive interest of molecular biologists in studying small RNAs and the epigenetic changes they cause in the inheritance of phenotypic traits.
The purpose of the study is to identify the level and directions of research on small RNAs capable of inducing pathological processes.
The source base of the study. Articles from scientific journals accessible through the PubMed search engine.
Research method. Analytical.
Results. The current level of understanding of epigenetic gene control mechanisms allows for targeted in vivo gene expression management and impact on future generations through epigenetic modifications. Hundreds of pathological conditions caused by interference with the epigenetic regulation of phenotypic traits have been identified. Technologies have been developed for the artificial introduction of specific small RNAs (sRNAs) into germ cells that are not “products” of maternal/paternal “genetic material.” These sRNAs accumulate in germ cells (oocytes, spermatozoa) and are transmitted to offspring after fertilization, i.e., to the next generation(s). sRNAs are known for their long-term stability and resistance to RNases. They can enter the human body through food, aerosol routes, parenterally (vaccines, DNA/RNA preparations) and be transmitted to subsequent generations.
Conclusions. The development of epigenetic gene control technologies carries unprecedented risks. Uncontrolled or malicious application of these tools could lead to catastrophic consequences, including:
- A sharp increase in pathologies in subsequent generations due to off-target effects that can be inherited;
- Disruption of the genetic stability of the human population due to unpredictable long-term consequences of interference with the epigenome;
- Targeted depopulation of specific ethnic groups or whole humankind.
About the Author
Ján LakotaSlovakia
Ján Lakota. MD, PhD.
Dubravska cesta 9, 841 04 Bratislava
References
1. Darwin C. The variation of animals and plants under domestication. London: John Murray; 1868.
2. van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19:213-28. https://doi.org/10.1038/nrm.2017.125
3. Su X, Wang H, Li Q, Chen Z. Extracellular Vesicles: A Review of Their Therapeutic Potentials, Sources, Biodistribution, and Administration Routes. Int J Nanomedicine. 2025;20:3175-99. https://doi.org/10.2147/IJN.S502591
4. Hu M, Han Y, Zhang X, Tian S, Shang Z, Yuan Z, et al. Extracellular vesicles for targeted drug delivery: advances in surface modification strategies and therapeutic applications. J Transl Med. 2025;23:1028. https://doi.org/10.1186/s12967-025-07077-y
5. Zhang J, Wu J, Wang G, He L, Zheng Z, Wu M, et al. Extracellular Vesicles: Techniques and Biomedical Applications Related to Single Vesicle Analysis. ACS Nano. 2023;17(18):17668-98. https://doi.org/10.1021/acsnano.3c03172
6. van Niel G, D'Angelo G, Raposo G, Rilla K, Tahara H, Théry C, et al. The power of imaging to understand extracellular vesicle biology in vivo. Nat Methods. 2021;18(9):1013-26. https://doi.org/10.1038/s41592-021-01206-3
7. Liu Y. Darwin's Pangenesis and the Lamarckian Inheritance of Acquired Characters. Adv Genet. 2018;101:115-44. https://doi.org/10.1016/bs.adgen.2018.05.005
8. Liu Y. Natural Selection and Pangenesis: The Darwinian Synthesis of Evolution and Genetics. Adv Genet. 2018;102:121-42. https://doi.org/10.1016/bs.adgen.2018.05.010
9. Harris I, Immler S, Chapman T, Maklakov AA. Selection on the epigenome: small RNA inheritance in animal evolution. Trends Genet. 2025;41(9):804-16. https://doi.org/10.1016/j.tig.2025.04.007
10. Vogt MC, Hobert O. Starvation-induced changes in somatic insulin/IGF-1R signaling drive metabolic programming across generations. Sci Adv. 2023;9(14):eade1817. https://doi.org/10.1126/sciadv.ade1817
11. Ivimey-Cook ER, Sales K, Carlsson H, Immler S, Chapman T, Maklakov AA. Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans. Proc Biol Sci. 2021;288(1950):20210701. https://doi.org/10.1098/rspb.2021.0701
12. Supotnitskiy MV. mRNA Technologies Danger. Journal of NBC Protection Corps. 2024;8(3):205-31 (In Russian). https://doi.org/10.35825/2587-5728-2024-8-3-205-231
13. Haase AD. An introduction to PIWI-interacting RNAs (piRNAs) in the context of metazoan small RNA silencing pathways. RNA Biol. 2022;19(1):1094-102. https://doi.org/10.1080/15476286.2022.2132359
14. Chen LL, Kim VN. Small and long non-coding RNAs: Past, present, and future. Cell. 2024;187(23):6451-85. https://doi.org/10.1016/j.cell.2024.10.024
15. Zhang M, Lu Z. tRNA modifications: greasing the wheels of translation and beyond. RNA Biol. 2025;22(1):1-25. https://doi.org/10.1080/15476286.2024.2442856
16. Pliatska V, Loher P, Magee R, Telonis AG, Londin E, Shigematsu M, et al. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects. Nucleic Acids Res. 2018;46(D1):D152-D159. https://doi.org/10.1093/nar/gkx1075
17. Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, et al. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science. 2016;351(6271):391-96. https://doi.org/10.1126/science.aad6780
18. Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L, Tavazoie SF. Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell. 2015;161(4):790-802. https://doi.org/10.1016/j.cell.2015.02.053
19. Holmes AD, Chan PP, Chen Q, Ivanov P, Drouard L, Polacek N, et al. A standardized ontology for naming tRNA-derived RNAs based on molecular origin. Nat Methods. 2023;20(5):627-8. https://doi.org/10.1038/s41592-023-01813-2
20. Sur S, Pal JK, Shekhar S, Bafna P, Bhattacharyya R. Emerging role and clinical applications of circular RNAs in human diseases. Funct Integr Genomics. 2025;25(1):77. https://doi.org/10.1007/s10142-025-01575-4
21. Yang L, Wilusz JE, Chen LL. Biogenesis and Regulatory Roles of Circular RNAs. Annu Rev Cell Dev Biol. 2022;38:263-89. https://doi.org/10.1146/annurev-cellbio-120420-125117
22. Margvelani G, Maquera KAA, Welden JR, Rodgers DW, Stamm S. Translation of circular RNAs. Nucleic Acids Res. 2025;53(1):gkae1167. https://doi.org/10.1093/nar/gkae1167
23. Zhang J, Zhao F. Circular RNA discovery with emerging sequencing and deep learning technologies. Nat Genet. 2025;57(5):1089-102. https://doi.org/10.1038/s41588-025-02157-7
24. Baugh LR, Day T. Nongenetic inheritance and multigenerational plasticity in the nematode C. elegans. Elife. 2020;9:e58498. https://doi.org/10.7554/eLife.58498
25. Jones BC, Wood JG, Chang C, Tam AD, Franklin MJ, Siegel ER, et al. A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan. Nat Commun. 2016;7:13856. https://doi.org/10.1038/ncomms13856
26. Liu S, Sharma U. Sperm RNA Payload: Implications for Intergenerational Epigenetic Inheritance. Int J Mol Sci. 2023;24(6):5889. https://doi.org/10.3390/ijms24065889
27. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci. 2014;17(1):89-96. https://doi.org/10.1038/nn.3594
28. Szyf M. Lamarck revisited: epigenetic inheritance of ancestral odor fear conditioning. Nat Neurosci. 2014;17(1):2-4. https://doi.org/10.1038/nn.3603
29. Mulligan CJ, Quinn EB, Hamadmad D, Dutton CL, Nevell L, Binder AM, et al. Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees. Sci Rep. 2025;15:5945. https://doi.org/10.1038/s41598-025-89818-z
30. Quinn EB, Hsiao CJ, Maisha FM, Mulligan CJ. Low birthweight is associated with epigenetic age acceleration in the first 3 years of life. Evol Med Public Health. 2023;11(1):251-61. https://doi.org/10.1093/emph/eoad019
31. Bédécarrats A, Chen S, Pearce K, Cai D, Glanzman DL. RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia. eNeuro. 2018;5(3):ENEURO.0038-18.2018. https://doi.org/10.1523/ENEURO.0038-18.2018
32. Lakota J, Jagla F, Pecháňová O. Heart memory or can transplanted heart manipulate recipients brain control over mind body interactions? Act Nerv Super Rediviva. 2021;63:49-51.
33. Burton NO, Greer EL. Multigenerational epigenetic inheritance: Transmitting information across generations. Semin Cell Dev Biol. 2022;127:121-32. https://doi.org/10.1016/j.semcdb.2021.08.006
34. Yap YS, Patrizio P, Cimmino L, Sdrimas K, Telonis AG. The Small Non-Coding RNA Profile of Human and Mouse Sperm. Noncoding RNA. 2025;11(1):15. https://doi.org/10.3390/ncrna11010015
35. Mehta P, Singh R. The composition of human sperm sncRNAome: a cross-country small RNA profiling. Reprod Biol Endocrinol. 2025;23:36. https://doi.org/10.1186/s12958-025-01358-3
36. Pavelka J, Poláková S, Pavelková V, Galeta P. An epigenetic change in a moth is generated by temperature and transmitted to many subsequent generations mediated by RNA. PLoS One. 2024;19(3):e0292179. https://doi.org/10.1371/journal.pone.0292179
37. Herridge RP, Dolata J, Migliori V, de Santis Alves C, Borges F, Schorn AJ, et al. Pseudouridine guides germline small RNA transport and epigenetic inheritance. Nat Struct Mol Biol. 2025;32(2):277-86. https://doi.org/10.1038/s41594-024-01392-6
38. Lin TY, Mehta R, Glatt S. Pseudouridines in RNAs: switching atoms means shifting paradigms. FEBS Lett. 2021;595(18):2310-22. https://doi.org/10.1002/1873-3468.14188
39. Kierzek E, Malgowska M, Lisowiec J, Turner DH, Gdaniec Z, Kierzek R. The contribution of pseudouridine to stabilities and structure of RNAs. Nucleic Acids Res. 2014;42(5):3492-501. https://doi.org/10.1093/nar/gkt1330
40. Li X, Ma S, Yi C. Pseudouridine: the fifth RNA nucleotide with renewed interests. Curr Opin Chem Biol. 2016;33:108-16. https://doi.org/10.1016/j.cbpa.2016.06.014
41. Granados-Riveron JT, Aquino-Jarquin G. Engineering of the current nucleoside-modified mRNA-LNP vaccines against SARS-CoV-2. Biomed Pharmacother. 2021;142:111953. https://doi.org/10.1016/j.biopha.2021.111953
42. Mulroney TE, Pöyry T, Yam-Puc JC, Rust M, Harvey RF, Kalmar L, et al. N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. Nature. 2024;625(7993):189-94. https://doi.org/10.1038/s41586-023-06800-3
43. Rabbani M, Zheng X, Manske GL, Vargo A, Shami AN, Li JZ, et al. Decoding the Spermatogenesis Program: New Insights from Transcriptomic Analyses. Annu Rev Genet. 2022;56:339-68. https://doi.org/10.1146/annurev-genet-080320-040045
44. Tirumalasetty MB, Bhattacharya I, Mohiuddin MS, Baki VB, Choubey M. Understanding testicular single cell transcriptional atlas: from developmental complications to male infertility. Front Endocrinol (Lausanne). 2024;15:1394812. https://doi.org/10.3389/fendo.2024.1394812
45. Kong W, Wei Y, Dong Z, Wang Z, Li J, Liu Y, et al. Role of size, surface charge, and PEGylated lipids of lipid nanoparticles (LNPs) on intramuscular delivery of mRNA. J Nanobiotechnol. 2024;22:553. https://doi.org/10.1186/s12951-024-02812-x
46. Kong W, Wei Y, Dong Z, Liu W, Zhao J, Huang Y, et al. Role of size, surface charge, and PEGylated lipids of lipid nanoparticles (LNPs) on intramuscular delivery of mRNA. J Nanobiotechnology. 2024;22(1):553. https://doi.org/10.1186/s12951-024-02812-x
47. McCutcheon SR, Rohm D, Iglesias N, et al. Epigenome editing technologies for discovery and medicine. Nat Biotechnol. 2024;42:1199–217. https://doi.org/10.1038/s41587-024-02320-1
48. Roth GV, Gengaro IR, Qi LS. Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications. Cell Chem Biol. 2024;6:S2451-9456(24)00309-X. https://doi.org/10.1016/j.chembiol.2024.07.007
Review
For citations:
Lakota J. Epigenetics and a new era of biological weapons. Journal of NBC Protection Corps. 2025;9(4):305-321. https://doi.org/10.35825/2587-5728-2025-9-4-305-321
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