Page 17 - Hormel Report 2021

conduct a comprehensive assessment of the capacity of major APCs, particularly dendritic cell (DCs), loaded with EV-AAVs to contribute to a vector associated immunity in several newly developed in vivo models. The significance of our study is a rational development of a new powerful platform for the next generation of AAV vectors based gene therapy with an optimal balance of effectiveness and safety.
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Publications:
• Karina Krotova and George Aslanidi. Modifiers of Adeno-Associated Virus- Mediated Gene Expression in Implication for Serotype-Universal Neutralizing Antibody Assay. Human Gene Therapy. 31(19-20):1124-1131, 2020.
• Yanerys Colon-Cortes, Mutasim Abu Hasan, George Aslanidi. Intra-tracheal Delivery of AAV6 Vectors Results in Sustained Transduction in Murine Lungs without Genomic Integration. GENE (Elsevier), 31; 5: 100037, 2020.
• Karina Krotova, Andrew Day, George Aslanidi. Engineered AAV6 based Vaccine Induces High Cytolytic Anti- Tumor Activity by Direct Targeting of Dendritic Cells and Improved Antigen Presentation, Molecular Therapy – Oncolytics, 7; 15: 166-177, 2019.
S669
S663
T665 K66
Improved intracellular trafficking
Heparin binding
T722
T251 6
S47
HI loop escape from endosome
K707
2 S49
9
Y445 S551 S45
5
T492 Y73
Y705 1
K53 1
Figure 1: 3-D stricture of adeno-associate virus. Alteration of the marked positions increase effectiveness of the virus.
Current research projects:
1. Optimization of Production and Validation of Rationally Designed AAV Vectors for Cockayne Syndrome Gene Therapy.
2. Evaluation of therapeutic potential of AAV vaccine on companion dogs with spontaneous oral melanoma.
3. Studying of Mechanism of high-efficiency transduction of hepatocytes by optimized AAV vectors by looking into major cellular pathways involved in life cycle of AAV vectors and vector associated immunogenicity.
4. Development of Vector Core for pre-clinical AAV Vectors Production and Toxicology Evaluation to help UMN and Mayo Clinic researchers with FDA IND applications.
5. Development of exosome protected AAV-based cancer vaccine to evaluate interaction with major subsets of dendritic cell, boost re-administration and efficacy in in vivo model.
6. Overcoming barriers to lung-directed gene delivery by develop- ment limited recombinant AAV library and validation of the most efficient vector in in vivo and NHP in vivo model for mucus penetration, reduced immunogenicity and lung tropism.
Figure 2: TEM image of the extracellular vehicle contained Adeno-associated virus particles.