**20. Characteristics of oncolytic viruses**

Viruses are microscopic particles that selectively replicate in the interior milieu of host cells, and inflammation and underlying pathogenicity can be associated with viral infection [143]. During the last decades, viruses have been employed in delivery of therapeutic genes for the treatment of metabolic and degenerative

illnesses, immunization against infectious diseases, and as oncolytic agents for cancer therapy [140].

The genome, which is either single-stranded or double-stranded RNA or DNA; the capsid, which is a protein coat that covers the genetic material; and the capsid, which is a protein coat that covers the genetic material, also in certain viruses, the lipidic envelope which surrounds the capsid and may enhance virus adhesion to host cell membranes, so increasing viral penetration, are the three major structural parts of most viruses. Oncolytic viruses have been developed over the last decade using both DNA and RNA viruses. DNA viruses offer several advantages: their huge genomes can be altered without interfering with viral replication; big eukaryotic transgenes may be incorporated by DNA viruses to boost therapeutic effectiveness or immunological regulation; DNA viruses express high fidelity DNA polymerases, assuring viral genome integrity and effective replication; and there is little, if any, nuclear integration of DNA viruses **Table 8** [144]. RNA viruses offer additional advantages: because they are smaller than DNA viruses, they can pass the blood–brain barrier, allowing tumors in the central nervous system to be targeted [145]. Despite the fact that their short genome restricts their capacity to encode big transgenes, because pre-existing tolerance to certain RNA viruses is poor in humans, viruses are more suited for systemic distribution, at least for the brief period before antiviral immunity is generated. Furthermore, the detection of viral double-stranded RNA by protein kinase R (PKR) that happens in normal cells may not occur in tumor cells, which often have lower levels and phosphorylation of PKR [146, 147]. Many aspects influence the selection of oncolytic viruses for tumor immunotherapy, in particular high pathogenicity, immunogenicity, cancer tropism, the potential to encode therapeutic transgenes, feasible viral concentration during synthesis, and durability. The active phase of viral infection and reproduction in host cells is described by the lytic virus life cycle [148]. Attachment, penetration and uncoating, synthesis, assembly, and release are the five different phases of the viral life cycle, which may be managed by genetic modification of the viral genome and can serve as a physiologically realistic strategy for selectively targeting tumor


#### **Table 8.**

*Characteristics of oncolytic virus.*

cells for infection and viral replication. Viruses also display pathogenicity and immunogenicity, which vary depending on viral species, dosage, mode of administration, pre-existing host immunity, and other variables, and are characteristics that can produce effective antitumor immunity.
