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Adeno-associated Virus-based mRNA Delivery System for Biologics

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At CD Formulation, we recently pushed out a novel adeno-associated virus-based mRNA delivery platform. This novel platform is able to not only combine the properties of both adeno-associated viruses and mRNA but also achieve high effective mRNA delivery. We also provide highly qualified adeno-associated virus vectors and much more services utilizing mRNA delivery systems to assist our customers' biological nanoformulation research and project development.

Advantages of Adeno-associated Virus (AAV) as a mRNA Delivery Vector

Here, we explore and describe that the adeno-associated virus vector consists of a protein shell. This protein shell is composed of the capsid of the AAV viral vector and the AAV genome.

Fig.1 The structure of adeno-associated virus genomic.Fig.1 Schematic representation of AAV genomic structure. (Arvind Srivastava, et al. 2021)

Adeno-associated virus vectors, as replication-defective viruses, have great potential in mRNA delivery systems because of their significant and unique benefits as follows.

  • Low toxicity
  • Low immunogenicity
  • Long transgene expression time
  • High stability
  • They have a wide range of cell types that can be infected. 
  • Effectively transfects dividing and non-dividing cells, multiple tissues in vivo.
  • Different AAV serotypes and variants provide flexibility in developing prime or boost regimens.
  • Altering the properties of the AAV capsid can avoid eliciting anti-capsid neutralizing immune responses after prime.

Applications of Adeno-associated Virus Vectors in mRNA Therapy

Adeno-associated virus vectors have widespread applications in vaccine therapy, protein replacement therapy, and chimeric antigen receptor T cell therapy. Recombinant adeno-associated viruses have been verified as therapeutic tools for a variety of diseases, such as ocular, neurological, metabolic, hematological, neuromuscular, cardiovascular disease, and oncology.

Fig.2 Clinical applications of recombinant adeno-associated viruses in gene therapy.Fig.2 Current clinical applications of rAAV in major human diseases. (Jiang-Hui Wang, et al. 2024)

Our Solution for Adeno-associated Virus-based mRNA Delivery System

At this platform, adeno-associated virus vectors are easy to achieve tissue-specific delivery. At CD Formulation, our core team has explored devise strategies for adeno-associated virus-based mRNA delivery to achieve better transduction efficiency and tissue specificity. Our workflow of adeno-associated viral vector development includes plasmid development and production, cell expansion, plasmid transfection, viral vector production, purification, filling, and finishing.

Plasmid Development and Production

At this stage, our workflow mainly includes the design and production of cis-plasmids, trans-plasmids, and helper plasmids.

Cell Expansion

During cell expansion, we used a HEK293-based transient transfection process for viral vector production.

Plasmid Transfection

The method used during our plasmid transfection is transient tri-transfection of mammalian cells or infection of mammalian cells and insect cells.

AAV Vial Vector Production

Our most common method of producing AAV viral vectors is transient transfection.

AAV Viral Vector Purification

Our purification of viral particles from process- and product-related impurities includes host cell material, plasmid DNA, and empty capsids. And our viral vector purification methods include cell lysis, filtration, platform purification method, and separation of empty capsids from full capsids.

AAV Viral Vector Formulation, Fill/Finish

Our viral vector formulation and fill/finish processes include formulation design, concentration, and diafiltration using transient flow filtration (TFF) to final formulation and fill/finish.

Fig.3 Our adeno-associated virus vector production process.Fig.3 Viral vector manufacturing process workflow, which involves various upstream, downstream, formulation, and fill/finish steps. (Arvind Srivastava, et al. 2021)

Why Choose CD Formulation?

  • With our novel delivery platforms, we have highly focused on designing, researching, and constructing adeno-associated virus-based mRNA delivery systems for biologics.
  • We can provide customer service and support about customizing adeno-associated virus vectors for mRNA delivery.
  • We also have extensive experience in the preparation methods of adeno-associated virus vector mRNA delivery, aiming to achieve precise targeted delivery of mRNA.

Published Data

Technology: Virus-derived mRNA delivery system

Journal: Small

IF: 13.0

Published: 2024

Results:

The authors describe that the viral vectors cover adenovirus, lentivirus (LV), and adeno-associated virus. The authors have also studied the properties and applications of AAVs. They have become the main research field of viral vectors due to their advantages, such as low genotoxicity, low immunogenicity, and high delivery efficiency. From this study, the authors have found that AAV vectors are naturally non-pathogenic and replication-deficient. So AVV is used as a vector for the production of transgenic proteins, which can effectively deliver mRNA in vivo to achieve the purpose of gene therapy.

Fig.4 Adeno-associated virus-derived mRNA delivery system for gene therapy.Fig.4 Virus-derived mRNA delivery system. (Menghao Yin, et al. 2024)

CD Formulation is specialized in researching our leading mRNA delivery system based on adeno-associated virus. This system includes the construction and analysis of adeno-associated virus vectors. If you have any questions about this system, please kindly contact us for in-depth discussion and communication.

References

  1. Arvind Srivastavaa, Krishna M.G. Mallelab, Nandkumar Deorkar, et al. Manufacturing challenges and rational formulation development for AAV viral vectors. Journal of Pharmaceutical Sciences. 2021,110:2609-2624.
  2. Jiang-Hui Wang, Dominic J. Gessler, Wei Zhan, et al. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Signal Transduction and Targeted Therapy. 2024,9:78.
  3. Menghao Yin, Hanruo Sun, Yanan Li, Jg, et al. Delivery of mRNA Using Biomimetic Vectors: Progress and Challenges. Small. 2024,2402715.
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