"The world's major killers are killers because they elude immune attack: HIV, malaria, tuberculosis," etc. What are needed are new approaches to stopping these pathogens. "The don't work because they haven't worked" - and what I mean by that is that the immune system is gonna fail when attacked by these pathogens, so trying to fix it with traditional methods is inherently a poor solution.
Let's reprogram the immune system using gene therapy to direct synthesis though the immune system of monoclonal antibodies or TCRs; let's not rely on its natural detection and synthesis.
Modify hematopoietic stem cells (from which derive all blood cells) so that our reprogramming is widely effective.
Program T cells for anti-tumor immunity:[presented too quickly to summarize]
Safety Concerns (gene therapy):
three of nine childre who received sucessful gene therapy for the X-SCID disease develiped leukemia... but maybe that was an effect of X-SCID, and not of the lentiviruses.
Consider selective inhibition of CCR5 in primary CD4 T-cells by siRNA introduced by the lentivirus vector - in principle, if no T-cells express CCR5, then none should be infected by HIV.
This will be a grand challenge to implement in humans (but none are really conceptual, just technical). We won't go into them.
Targeting of lentivirus vectors (lentivectors):
Infection has two components:
1)Binding/entrance into the cell, and 2)endosomal membrane fusion. One thing that will bind nicely to some cell surface protein (like CD20) is an antibody. Lentiviruses, and all retroviruses, envelope themselves with the surface of the cell they infect, so if you modify host cells to express a membrane-bound antibody, lentiviruses that infect and bud off from them can be targeted to whatever host receptor that antibody binds.