Friendly fire: redirecting herpes simplex virus-1 for therapeutic applications

Area of Science:

• Virology
• Gene Therapy
• Oncolytic Virotherapy

Background:

• Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus with a large genome encoding numerous proteins.
• Understanding HSV-1 protein functions enables genetic engineering for therapeutic applications.
• Attenuated HSV-1 mutants are crucial for developing novel gene therapy strategies.

Purpose of the Study:

• To review the progress in creating attenuated genetically engineered HSV-1 mutants for gene therapy.
• To differentiate between replication-competent and replication-defective HSV-1 mutants.
• To highlight the specific applications of each mutant type in therapeutic interventions.

Main Methods:

• Genetic engineering of HSV-1 to create specific viral mutants.
• Categorization of mutants based on replication competence (non-essential gene deletion) or defectiveness (essential gene deletion).
• Review of existing literature on the use of these mutants in preclinical and clinical studies.

Main Results:

• Attenuated HSV-1 mutants can be engineered to be either replication-competent or replication-defective.
• Replication-competent HSV-1 mutants show promise as oncolytic viruses for selective tumor cell destruction.
• Replication-defective HSV-1 mutants serve as effective delivery vectors for replacement gene therapy, efficiently infecting both quiescent and dividing cells and accommodating large transgenes.

Conclusions:

• Genetically engineered HSV-1 mutants represent a versatile platform for gene therapy.
• The choice between replication-competent and replication-defective strategies depends on the specific therapeutic goal.
• HSV-1 vectors offer significant advantages, including broad infectivity and large transgene capacity, for various gene therapy applications.