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Anti-angiogenic gene therapy
A myriad of novel bioactive proteins are currently being discovered. These proteins
have complex structures and native forms in vivo and show strong efficacy against various diseases.
To validate the in vivo biological activities of these proteins requires an elaborate series of
reactions to process them as biopharmaceuticals. Gene therapy is the currently favored trend for administering
DNA encoding such biologically active proteins in vivo and for the treatment of diseases in situ
through the expression of gene therapy vectors in the body. Gene therapy therefore eliminates the complicated
requirements for the production and downstream processing of a protein drug agent, and furthermore, it is
expected to improve the efficacy of such drugs, the activities of which are frequently sub-optimal when
administered in vivo. Employing an AAV vector system, we are now focusing on the development of gene
therapeutics against cancer.
 Vectors derived
from adeno-associated virus (AAV) are known to be a promising delivery vehicle for human gene therapy, and thus
numerous investigations to treat diseases are now under way using these viral vectors. AAV is a dependent human
parvovirus that cannot replicate itself and requires helper functions from other viruses, such as adenovirus,
to mediate productive infection. AAV therefore offers many advantages e.g. it is non-pathogenic in humans, it
transduces well in both dividing and non-dividing cells of multiple tissue origins and it prominently mediates
long-term gene expression, persisting in the infected cell as either an integrated provirus or in an episomal
form.
Scalable rAAV Production Process
Our unique and robust suspension-transfection technology ensures easy production of a large quantity of
high-quality recombinant AAV vectors that are required for preclinical and clinical studies.
• Direct transfection to suspended cells cultured in a bioreactor
• Suspension culture of HEK 293 cells
• Production of 1013 physical particles or
1011 infectious particles of rAAV in 2L scale
• Efficient purification protocol
Metastatic Tumors
LK, a cryptic fragment of apolipoprotein (a), is a novel antiangiogenic agent that actively causes regression
of a number of both solid and metastatic tumors. rAAV-LK is thus a promising second-generation gene therapeutic
agent that will ensure long-term effects without the need for the frequent and high load administration of the
LK protein. As shown above, LK68 and LK8, generated by rAAV-LK68 and rAAV-LK8, respectively, significantly
decreased the number of B16F10 nodules in the lung, further demonstrating the potential anti-metastatic activity
of LK. Further investigations of their activity is under way in animal tumor models other than melanoma.
Publications
Lee, K., Kim, Y. -G., and Jo, E. -C. (2003). Shuttle PCR-based cloning of the infectious adeno-associated virus
type 5 genome. J. Virol. Methods 111: 75-84.
[PubMed Citation] |
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