Adeno-associated Virus (AAV) Vectors

Adeno-Associated Virus (AAV) vectors are currently among the most frequently used viral vectors for gene delivery and manipulation both in vitro and in vivo. Its highly efficient gene transfer capability, existence of multiple serotypes for selective organ/tissue targeting, and safety profile, make AAV the vector of choice. Our extensive collaborations with clients in different therapeutic areas have provided us with experiences on AAV vector based gene manipulation in a variety of animal disease models.

General Adeno-associated Viral Vector (AAV) Platforms

  • Customized recombinant AAV (rAAV) genome construction and validation
  • General AAV packaging, purification and tittering
  • Premade AAV control vectors
Fig 1. Customized recombinant AAV (rAAV) genome construction
Fig 2. In vitro validation by two clinically-relevant rAAV vectors

AVV Vectors development

  • Customized therapeutic rAAV vector design, construction and packaging
  • In vitro validation of the therapeutic effect
  • Dose-escalation long-term efficacy and safety evaluation in vivo including wild type and disease models
Fig 3. Schematic diagram of AAV-mediated Gene Replacement Therapy
Fig4. Efficacy and safety evaluation of AAV8-Gene A in vivo.
a. Biodistribution of AAV8-GFP in mice.
b. Transduction efficiency of AAV8-GFP vector in liver.
c. Gene A expression levels in mice at week 1, 2, 4, 6 and 8 post viral delivery.
d. No alanine transaminase (ALT) change demonstrate the safety of the gene delivery. 

AAV-mediated In Vivo Genome Editing

  • Customized rAAV vector design , construction and packaging for in vivo genome editing
  • In vitro validation of genome editing
  • In vivo genome editing efficiency and functional evaluation
Fig 5. Schematic diagram of in vivo genome editing and therapy

 
Fig 6. Validation of in vivo KO by AAV8-sgGene B. a, Editing efficiency of AAV8-sgGene B. b, Representative indels formation in liver tissue.

Screening Services

With the high quality AAV vector products, WuXi Biology conducts the following research services to help our clients on target validation, gene function screen, animal model development and therapeutic studies under different disease conditions.

Target validation in multiple animal disease models:

AAV vector can be used as an effective tool for target validation in different therapeutic areas including metabolic diseases, oncology, inflammation, CNS, kidney diseases, cardiovascular diseases, and infectious diseases.

Biologicals screen:

AAV vector can mediate over-expression of target gene either systemicly or in an organ/tissue specific manner. The gene product in situ will gain biological activity with endogenous modifications. The therapeutical potential of the gene products can thus be rapidly screened in established animal models.

Model development:

Animal models can be developed by manipulation of disease-associated genes in animals (over-expression, knockdown).