Advances in foamy virus vector systems: Development and applications

Foamy virus (FV) is a retrovirus with a safer integration profile than other retroviruses, rendering it appealing for gene therapy. Prototype FV (PFV) vector systems have been devised to yield high-titer vectors carrying large transgenes. Subsequent iterations of PFV vectors have been engineered to be replication-incompetent, enhancing their safety. A third generation PFV vector system, composed of four plasmids, has been adapted to accommodate large transgenes. Additionally, a novel dual-vector system shows promise for convenient and efficient gene delivery, particularly with the forthcoming development of stable producer cell lines expressing PFV Env. FVs exhibit a broad host spectrum due to the ubiquitous presence of the host factor, heparan sulfate (HS), on their surface. The receptor-binding domain (RBD) of FV Env proteins plays a crucial role in binding to the host cell HS. The FV vector system has been employed in hematopoietic stem cell (HSC) gene therapy to address monogenic diseases in dog and mouse models. In addition, FV vectors safely and efficiently deliver anti-HIV transgenes to HSCs, and vectors carrying HIV epitopes successfully induce antibodies against HIV, offering the promise of anti-HIV gene therapy and vaccine development. In this review, we delve into the development and utilization of FV vector systems, emphasizing their unique advantages in gene therapy, including their non-pathogenic nature, broad host tropism, large transgene capacity, and persistence in resting cells. Furthermore, we discuss the potential of FV vectors in tackling current challenges in gene therapy and their viability as valuable tools for treating genetic diseases.