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This profound shift has also reshaped the landscape of live attenuated vaccine (LAV) development in contrast to conventional methods. Here we explore how modern molecular strategies have superseded previous empirical approaches, moving toward deliberate genetic modifications that both enhance and balance the aspects of LAV safety, stability, and potent immunogenicity. By detailing the transition from classical approaches to targeted, molecular\u2010driven attenuation, our work reviews how advanced genetic methods address historical limitations and expand the potential for vaccine design. Hence, the current paper bridges the gap between foundational vaccine practices and cutting\u2010edge biotechnology, offering a comprehensive perspective on the progression of molecular genetic strategies on LAV development and its future trajectory. The paper also elaborates on the key challenges of raising LAVs to clinical standards while describing in tandem the genetic approaches to overcome the limitations. Critical performance factors governing the LAV market and clinical deployment, alongside the pivotal role of artificial intelligence in refining LAV rational design, are also further discussed.<\/jats:p>","DOI":"10.1002\/biot.70185","type":"journal-article","created":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T09:19:21Z","timestamp":1771147161000},"source":"Crossref","is-referenced-by-count":1,"title":["Molecular Genetics as the Leading\u2010Edge Approach in Driving the Development of Live Attenuated Vaccines"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-7855","authenticated-orcid":false,"given":"Ramesh","family":"Thevendran","sequence":"first","affiliation":[{"name":"Faculty of Applied Science Department of Biotechnology AIMST University  Bedong Kedah Malaysia"},{"name":"Centre of Excellence for Nanotechnology and Nanomedicine (CoExNano) AIMST University  Bedong Kedah 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