Other Hereditary Disease

In the past, recombinant vectors based on a non-pathogenic parvovirus, adeno-associated virus (AAV), have taken center status as a gene delivery system for potential gene therapy of many human diseases. In particular, AAV-mediated gene therapy has become an attractive, curative approach to treat inherited deficiencies in clinical applications. As a well-recognized provider in the gene therapy, Creative Biolabs is absorbed in AAV biology, viral structure, cell entry mechanisms, and is skilled at designing AAV vehicles with specific tissue tropism and high delivery efficiency. For hereditary diseases, we provide rational design and optimal services to create AAV gene transfer products, achieved by manipulating different serotypes and capsid engineering.

Overview

Hereditary disease is a class of genetic disorders that can be passed on from one generation to another through defective genes. It is inherited genetically but cannot be easily cured by traditional methods. Gene therapy has entered clinical practice with marketing authorizations for patients with inherited diseases, including inborn blindness, adenosine deaminase (ADA) deficiency, mucopolysaccharidosis type VI, and Crigler-Najjar syndrome. AAV vehicles are currently among the most frequently used viral vectors for gene therapy. This system has been established as the preferred vector of choice in hereditary diseases due to its superior safety profile and non-integrative nature.

AAV Vector Design Services for Hereditary Diseases

Schematic representation of the most efficient capsid-modified next generation of rAAV serotype vectors. Figure 1. Schematic representation of the most efficient capsid-modified next generation of rAAV serotype vectors. (Büning, 2019)

AAV gene therapy is a new promising tool for treating a spectrum of inherited disorders by delivering therapeutic genes to specific tissues or organs. As known, appropriate AAV vector design is pivotal to the development of successful gene therapy, which commonly requires stable and long-lasting transgene expression in targeted cells while avoiding transgene-associated adverse effects, such as off-target effect, overexpression-related cytotoxicity, or immune response. Here, we list some services that have been successfully introduced for clients to study inherited diseases, including but not limited to:

Recombinant AAV (rAAV) vectors for gene therapy have been mostly based on AAV serotype 2 (AAV2). At Creative Biolabs, we have the capability to generate rAAV particles lacking any viral genes and containing a DNA sequence of interest. AAV2-based rAAV particles can transduce muscle, liver, retina, brain, and lung, needing some weeks for optimal expression. The transduction efficiency is depended on each step of rAAV infection, including binding, entry, viral trafficking, nuclear entry, uncoating, and second-strand synthesis. When dealing with hereditary diseases, our services can help you to address vector design challenges as below:

  • Engineering of the viral capsid to improve vector specificity
  • Optimized transduction protocols to increase efficiency
  • Re-directed vector tropism toward a target cell by combining insertion of a ligand with site-directed mutagenesis
  • QC analysis

AAV-mediated gene therapy has taken a leap towards clinical application in the last decade. As a reliable supplier in the gene therapy market, Creative Biolabs has rich experience in designing delivery tools and transgene expression cassettes by novel molecular engineering and directed evolution approach. Especially, we offer customized AAV vehicle services for the treatment of diseases ranging from rare genetic disorders to major public health concerns. For more information, please feel free to contact us or directly send us an online inquiry.

Reference

  1. Büning, H.; et al. (2019). Capsid modifications for targeting and improving the efficacy of AAV vectors. Mol Ther Methods Clin Dev. 12: 248-265.
For research use only. Not intended for any clinical use.