After small molecule drugs and therapeutic proteins, and with the first products on the market, gene therapy will be the next wave of medicines potentially capable of curing todays major diseases. Key to the success of gene therapy will be the safe and efficient delivery of the therapeutic genes to the proper cells of the body. Viruses evolve to efficiently transfer and express their genes in host cells. This ability renders them ideally suited for use as gene delivery vectors. Viral vectors that are currently used for gene therapy cannot be administered in vivo due to their instability (in the case of lentiviral vectors) or immunogenicity resulting in low transgene expression levels over time (in the case of AAV vectors).
Gene delivery vectors derived from Simian virus 40 (SV40) are an attractive alternative to lentiviral and AAV vectors for clinical gene therapy. SV40 is a polyomavirus that strictly replicates in its natural host, macaques, where it causes chronic asymptomatic infections. SV40 particles enter infected cells by an unique mechanism that enables them to evade exposure to the host immune system. Since humans can be considered naÏve to SV40, it is expected that SV40 vectors are non-immunogenic or tolerogenic when applied in clinical settings. The non-immunogenicity also named tolerogenicity in humans renders SV40 vectors highly attractive for use in gene therapy and immunotherapies.
We have adapted the SV40 genome used for the production of vector particles. In parallel we generated a novel Vero-based packaging cell line named SuperVero that exclusively expresses the SV40 large T antigen needed for replication of the vector genomes and for production of the capsid proteins. SuperVero cells produce similar numbers of SV40 vector particles to the currently used packaging cell lines, albeit in the absence of contaminating wild type SV40 particles. Our unique SV40 vector platform named SVec paves the way to clinically evaluate a whole new generation of SV40-based therapeutics for a broad range of important diseases.