Herpes simplex virus (HSV) is a common human pathogen, and humans are its natural hosts. Structurally, HSV viruses are spherical, with multilayered concentric structures. Because HSV can establish a latent infection in these cells, it is particularly well suited to deliver genes to neurons. Advances in molecular biology and viral genetics have made possible the use of viral vectors for gene therapy, whereby exogenous genes are packaged into such vectors that can be targeted to specific regions of the nervous system for the treatment of neurological disorders such as malignant gliomas, Parkinson's disease, known monogenic disorders, and cerebral ischemia. CD Formulation provides high-quality HSV vector development services for gene therapy delivery system development.
Recombinant HSV is an ideal viral vector for in vivo and in vitro gene transduction experiments in gene therapy research, and has multiple application advantages.
Selection of suitable genes as therapeutic targets, genes with important roles in herpes simplex virus type I infection, and disease progression are ideal for selection. The gene should have potential therapeutic effects and be modifiable.
Designing an HSV vector suitable for gene therapy requires knocking out certain essential genes of the virus to ensure that the virus is unable to replicate in normal cells while maintaining its ability to replicate in the target cells.
Modern gene editing techniques such as CRISPR-Cas9 are utilized to make precise modifications to the HSV genome, including the insertion of therapeutic genes and the removal of certain genes from the virus to reduce its virulence.
Recombinant HSV vectors are constructed by homologous recombination or bacterial artificial chromosome (BAC) technology, which allows manipulation of the viral genome in E. coli, while yeast artificial chromosome (YAC) technology supports replication and modification of the genome in yeast.
Viral vectors are produced in engineered cell lines. These cell lines are designed to support viral replication and packaging while expressing desired therapeutic genes.
Produced viruses undergo a purification step to ensure the quality and safety of the viral vector. This may include purification of the viral pellet using techniques such as sucrose density gradient centrifugation.
Gene delivery using HSV vectors is a frontier area for gene therapy applications. Recombinant HSV has a wide range of applications in neurological gene delivery, oncolytic gene transduction, and vaccine development.
Technologies & Platforms | Content Description |
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Gene synthetic technology platform | The target viral vectors constructed by the gene synthesis technique exhibited high infectivity as well as excellent replication ability at the cellular level. This technology has played a crucial role in the development of herpesvirus vectors, and we have been able to utilize this technology to help scientists edit and improve viral vectors with greater precision, thereby advancing the development and application of viral vectors in gene therapy. |
Viral vector modification technology platform | Using gene editing technology, we can modify HSV to improve its efficiency and safety as a vector. For example, with the CRISPR-Cas9 system, recombinant HSV-1 vectors can be rapidly constructed for oncolytic virus therapy and gene transfer in tumors. |
DNA recombination technology platform | Recombinant gene technology has made it possible to construct recombinant HSV vectors that can be used for gene therapy, vaccine development, and lysosomal virus therapy. For example, by inserting therapeutic genes or immunostimulatory factors (e.g., hGM-CSF expression cassettes) into HSV vectors, recombinant viruses with therapeutic potential for treating tumors can be developed. |
Technology: Gene synthetic technology
Journal: Virol Sin
IF: 3.2
Published: 2023
Results: HSV-1 H129 is a clinical isolate of herpes simplex virus type I with unique cis-trans-synaptic transmission properties, which has been widely used as a vector in the field of neural loop tracing. However, it is difficult to edit HSV-1 at the genome-wide level by conventional molecular biology methods, which limits the further application of HSV-1 virus. Using the neural tracer virus H129-G4 as a template, the team synthesized the whole genome of the virus with a green fluorescent gene in yeast using synthetic technology, and transfected it into mammalian cells, successfully rescuing H129-Syn-G2. The study demonstrated that the virus has similar infectivity and morphological characteristics as the parental virus, and its cellular level replication ability is better than that of the template virus.
Fig.1 Schematic flowchart of the synthesis of H129-Syn-G2. (Xiao H, et al., 2023)
CD Formulation as a global leader in scientific services, we provide innovative solutions to accelerate the development of HSV vectors to help advance the field of gene therapy. If you are interested in us, please feel free to contact us.
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