CD47-Free Viral Vector Production for Phagocyte Transduction
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Solution Overview
Problem
Existing gene therapy vectors face challenges in efficiently transducing professional phagocytes and antigen presenting cells due to the presence of CD47 molecules on their surface, which impede cell transduction and induce immune responses.
Innovation Solution
Genetically engineering cells to decrease the expression of CD47 on the surface, resulting in CD47-free enveloped viral particles that enhance gene transfer efficiency into professional phagocytes and antigen presenting cells, while increasing susceptibility to phagocytosis and cytokine response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If viral vectors are used for gene delivery to professional phagocytes and antigen presenting cells, then gene transfer capability is provided, but CD47 molecules on the viral surface impede transduction efficiency and induce immune responses
Solution Approach 1:
The patent applies the extraction principle by removing CD47 molecules from the viral vector surface through genetic engineering of producer cells. This elimination of the harmful surface protein resolves the contradiction by preventing immune recognition and phagocytic inhibition, thereby improving gene transfer efficiency to professional phagocytes and antigen presenting cells without triggering deleterious immune responses
2Ease of manufacture
If surface proteins are incorporated into viral envelopes during budding, then viral particle formation is achieved, but surface-exposed proteins may prevent transduction of certain cell types or trigger immune responses
Solution Approach 1:
The patent applies local quality by creating viral particles with modified surface properties specifically at the protein composition level. By genetically engineering producer cells to decrease CD47 expression, the resulting viral particles have altered local surface characteristics that enable transduction of specific cell types (professional phagocytes and antigen presenting cells) while maintaining overall viral particle formation and production efficiency
Data Source
AI summary
An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of CD47 on the surface of the cell.