This is the objective:
So the T and B cells, both of lymphoid origin, in the Adaptive Immune System are the Target Cells of this AAV vector therapy. These cells will be targeted and the DNA within these cells will be spliced into and the method to manufacture human monoclonal antibody Leronlimab will be genetically encoded into the DNA of those target cells, the T and B cells. That will be a permanent genetic change in that HIV patient. He/She will be permanently capable of manufacturing the human monoclonal antibody Leronlimab within his T and B cells indefinitely from then on.
When his T & B cells manufacture within their Endoplasmic Reticulum and Golgi bodies the protein antibody structure of leronlimab, it will be pushed out through the cell membrane by some mechanism and then it will attach and bind to the cells many CCR5 receptors. This will permanently CURE his HIV.
Yes, his T and B cells will be making LRM but they will be used to bind to the CCR5 receptors on the T cells b/c remember, the only way HIV replicates is through the CD-4 T cell receptor. It can hide and remain dormant everywhere else, but it can't replicate unless it invades a CD-4 T cell, so that is where LRM will bind to if it is to achieve a CURE.
Quote:Here, we are proposing to utilize our novel directed evolution technique to generate AAV vectors specific for T and B cells. These novel AAV vectors will facilitate in vivo delivery of Leronlimab expression here, but more importantly will support the future use of other anti-HIV approaches including CRISPR-Cas9, chimeric antigen receptors, and broadly neutralizing antibodies by delivering these therapeutics to the relevant immune cell type. In specific aim 1, we will generate and characterize AAV bearing capsids that target T and B cells specifically across both macaques and humans. In aim 2, we will demonstrate proof-of-concept utility of these new AAVs by delivering Leronlimab to SHIV-infected, ART suppressed macaques to determine if a functional cure can be achieved with this approach. This work would expand our knowledge of the mechanism of HIV cure by showing the utility of long-term antibody-based competitive CCR5 inhibition and establish a new set of AAV vectors to support in vivo delivery of anti-HIV therapeutics.
So the T and B cells, both of lymphoid origin, in the Adaptive Immune System are the Target Cells of this AAV vector therapy. These cells will be targeted and the DNA within these cells will be spliced into and the method to manufacture human monoclonal antibody Leronlimab will be genetically encoded into the DNA of those target cells, the T and B cells. That will be a permanent genetic change in that HIV patient. He/She will be permanently capable of manufacturing the human monoclonal antibody Leronlimab within his T and B cells indefinitely from then on.
When his T & B cells manufacture within their Endoplasmic Reticulum and Golgi bodies the protein antibody structure of leronlimab, it will be pushed out through the cell membrane by some mechanism and then it will attach and bind to the cells many CCR5 receptors. This will permanently CURE his HIV.
Yes, his T and B cells will be making LRM but they will be used to bind to the CCR5 receptors on the T cells b/c remember, the only way HIV replicates is through the CD-4 T cell receptor. It can hide and remain dormant everywhere else, but it can't replicate unless it invades a CD-4 T cell, so that is where LRM will bind to if it is to achieve a CURE.
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