| Criteria | Plasmid | Virus | Remarks |
| Definition | Small, circular or linear extrachromosomal DNA molecules found in bacteria and some eukaryotes | Infectious acellular entities composed of genetic material encased in a protein coat (capsid) | Plasmids are non-infectious, self-replicating DNA elements, while viruses are obligate intracellular parasites. |
| Structure | Circular or linear double-stranded DNA (rarely RNA), lacking a protein coat | DNA or RNA (single or double-stranded) enclosed in a protein capsid; some have lipid envelopes | Viruses are more complex structurally, designed for transmission and host infection. |
| Genetic Material | Usually double-stranded DNA (dsDNA); occasionally single-stranded DNA | Can be DNA or RNA; single or double-stranded, linear or circular | Plasmids are mostly DNA-based, while viruses show more diversity in nucleic acid type. |
| Replication | Autonomous replication within a host cell using host replication machinery | Replicates only inside a host cell after infection, hijacking host transcription/translation machinery | Plasmids can replicate independently, whereas viruses require host cell entry and uncoating. |
| Host Dependency | Depends on host cell for replication but not for transmission | Completely dependent on host for replication, transcription, translation, and assembly | Viruses lack all metabolic machinery and are strictly dependent on the host. |
| Mobility and Transfer | Transferred via conjugation, transformation, or transduction | Transmitted through infection, often involving receptor-mediated entry into host cells | Plasmids can be horizontally transferred without causing cell lysis; viruses often result in lytic or lysogenic cycles. |
| Pathogenicity | Generally non-pathogenic; may carry virulence or antibiotic resistance genes | Often pathogenic; cause diseases in plants, animals, and bacteria (e.g., bacteriophages) | Viruses are typically associated with diseases, while plasmids confer adaptive benefits. |
| Host Range | Limited to related bacterial strains or specific cell types | Wide range, depending on virus type — infects animals, plants, fungi, bacteria (bacteriophages) | Host specificity is determined by surface receptors in viruses and compatibility factors in plasmids. |
| Applications in Biotechnology | Used in genetic engineering, cloning, recombinant protein production | Used in gene therapy, vaccine delivery, viral vectors for CRISPR delivery | Both are powerful tools in molecular biology, with plasmids favored for stable cloning and viruses for efficient gene delivery. |
| Persistence in Host | May be stably maintained through generations (replicons) | May establish latency (e.g., herpesviruses) or be cleared after lytic infection | Plasmids are more stably maintained without necessarily harming the host. |
| Packaging | Not packaged; naked DNA molecules | Encased in a protein shell (capsid), sometimes with lipid envelope | This structural difference allows viruses to survive extracellularly; plasmids do not. |
| Size Range | 1 kb to >200 kb | ~20 nm to >300 nm in size; genome sizes range from 2 kb to >2.5 Mb (giant viruses) | Viral genome sizes vary more drastically; plasmids are relatively smaller. |
| Use in Gene Transfer | Artificial vectors (e.g., pUC, pBR322) engineered with selectable markers and origins | Viral vectors (e.g., lentivirus, adenovirus) engineered for transient or stable expression | Viral vectors offer higher transfection efficiency; plasmids are safer and easier to manipulate. |
| Immune Response Induction | Non-immunogenic (generally not recognized by host immune system) | Strongly immunogenic; triggers innate and adaptive responses | Viral delivery is efficient but limited by immune responses; plasmids are immunologically silent. |
