Rabies Virus

The development of gene therapy techniques that promote neuronal survival and protection provides effective therapeutic approaches for neurological and neurodegenerative diseases. Importantly, production of lentiviral vectors pseudotyped with rabies virus (RV) glycoproteins allows gene delivery into motor neurons and thus has significant potentials in gene therapy for neuronal diseases.

Introduction of Rabies Virus

RV is a single-stranded negative-sense RNA virus from the Rhabdoviridae family and has a wide range of host tropism, including humans, rodents and bats. RV causes central nervous system (CNS) infection, which is usually fatal. Like vesicular stomatitis virus (VSV), RV uses its envelope glycoprotein (RVG) to attach the host cell surface receptors and mediate viral entry. Besides, the receptors for RVG include the neurotrophic receptor (p75NTR), the neural cell adhesion molecule (NCAM) and nicotinic acetylcholine receptor (nAChR), which are all expressed on neural cells. The neuro-tropism of RVG makes it an attractive envelope to pseudotype lentiviral vectors (LVs) for transduction of neuronal cells.

The Pseudotyping of LVs with RVG

LVs used for CNS gene transfer are usually based on the human immunodeficiency virus type 1 (HIV-1). However, in the past few years, due to safety concerns, vectors derived from other lentiviruses, such as the non-primate equine infectious anemia virus (EIAV) and feline immunodeficiency virus (FIV), have been developed as gene transfer vectors to the CNS. Most of these vectors are pseudotyped with the VSV glycoprotein (VSVG) envelope protein. More recently, RVG and glycoproteins from other members of the Rhabdoviridae have been used in pseudotyped LVs.

RVG can pseudotype LVs, although its efficiency is lower than that of the VSVG. Pseudotyping of LVs with RVG (RV-LVs) confers both neurotropism and the ability to mediate retrograde trafficking of vector particles along neuronal axons. RVG co-localizes with its receptors, which shuttle to the neuronal soma via retrograde transport, allowing RV-LVs to access the nucleus. As RV and VSV are closely related, chimeric proteins created by fusing parts of VSVG and RVG can also pseudotype LVs. In particular, HIV-1-based LVs pseudotyped with fusion glycoprotein B type (FuG-B) or a variant of FuG-B (FuG-B2), in which the cytoplasmic domain of RVG is replaced by the corresponding part of VSVG, show efficient retrograde gene transfer into both spinal cord and hindbrain motor neurons. In addition, EIAV-based LVs pseudotyped with VSV-G and RVG are able to mediate stable and long-term transduction of neural cells in vitro and in vivo. In short, RV-LVs mediates the efficient transduction of neurons outside the body and in vivo.

Application of RV-LVs

RVG is the most promising glycoprotein for the targeting of neuronal cells in vitro and in vivo. It presents the possibility of targeting gene therapy for neurodegenerative diseases specifically to neuronal cells. Additionally, it opens up the possibility of a noninvasive administration of the vector by targeting the peripheral sites of neuromuscular synapses to target CNS neurons affected by diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy.

Creative Biolabs offers a broad range of customized LVs and high-quality LVs-based gene delivery services for your basic research and clinical applications with a reasonable cost and quick turnaround time. Our experienced experts will help you with any questions you may have about LVs in your research. For more information, please feel free to contact us.