Herpes Simplex Virus Oncolytic Therapy for Pediatric Malignancies

Developing oncolytic Herpes simplex virus type 1 through UL39 knockout by CRISPR-Cas9

Objective(s): Oncolytic Herpes simplex virus type 1 (HSV-1) has emerged as a promising strategy for cancer therapy. However, development of novel oncolytic mutants has remained a major challenge owing to low efficiency of conventional genome editing methods. Recently, CRISPR-Cas9 has revolutionized genome editing.Materials and Methods: I...

Development of a regulatable oncolytic herpes simplex virus type 1 recombinant virus for tumor therapy.

Oncolytic viruses are genetically modified viruses that preferentially replicate in host cancer cells, leading to the production of new viruses and, ultimately, cell death. Currently, no oncolytic viruses that are able to kill only tumor cells while leaving normal cells intact are available. Using T-REx (Invitrogen, Carlsbad, CA) gene switch technology and a self-cleaving ribozyme, we have cons...

Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes simplex virus-1 in children

Progress for improving outcomes in pediatric patients with solid tumors remains slow. In addition, currently available therapies are fraught with numerous side effects, often causing significant life-long morbidity for long-term survivors. The use of viruses to kill tumor cells based on their increased vulnerability to infection is gaining traction, with several viruses moving through early and...

Preclinical Evaluation of Engineered Oncolytic Herpes Simplex Virus for the Treatment of Pediatric Solid Tumors

Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV agains...

Potent Oncolytic Herpes Simplex Virus for the Therapy of Advanced Prostate Cancer