Progress Report
Creating A Society Whose Citizen’s Health is Monitored by Remote Control of Intracellular Cybernetic Avatars[2] Intracellular CA designs
Progress until FY2024
1. Outline of the project
The realization of a society that is monitored by the remote control of intracellular cybernetic avatars (hereinafter referred to as “intracellular CA”) requires (1) a function to detect cells that cause physical disorders, (2) a function to amplify the discovered information, (3) a function to convert the amplified information so that it can be detected outside the body, (4) a function to remove the causative cells, (5) a switch pathway that can drive or stop the function intracellular CA by remote control, and (6) a mechanism to grasp and achieve improvement through cooperation and coordination between cells carrying intracellular CA in the body. In this R&D Item, we will design and construct intracellular CAs with these functions above. The constructed intracellular CAs will be loaded onto the cells selected in accordance with R&D Item 5 using the technology described in R&D Item 3, and evaluated in cooperation with R&D Items 4, 5, and 6.
2. Outcome so far
In R&D Item 2, we set up R&D Items (2-1), (2-2), and (2-3) to realize (1), (4), and (6) on Outline of the project. In the same manner, to realize (2) and (3), R&D Items (2-1) and (2-3) and (2-2) were set up. (2-3), and (2-5) would co-operate with each other to realize (5). By this a multilayered R&D Items, the challenging problem of designing and constructing intracellular CAs would be tackled. To date, we have conducted the following research.
(2-1) We have designed and constructed several nano CAs utilizing nanoparticles and DNA. We constructed an intracellular CA with a signal conversion to light (Figure 1).
(2-2) As one of the compound-based intracellular CAs, we proceeded to introduce a switch that can “stop” cells by compound treatment. As a result, we have succeeded in inducing cell death (apoptosis) promptly by compound treatment (Figure 2).
(2-3) As one of the gene-based intracellular CAs, we utilized the phytohormone receptor genes to establish a technology platform for “starting” and conditionally “branching” the function of CA-loaded cells under culture conditions, and filed a patent application (Figure 3).
(2-4) We developed a plasma membrane channel-like intracellular CA using a synthetic DNA structure as an “forced shutdown” function for CA-loaded cells. As a result, we succeeded in establishing design scheme for intracellular CAs to efficiently induce cell death by membrane channel-like structure (Figure 4).
By providing these deliverables, intracellular CAs, to R&D Items 4, 5, and 6, we have started experiments to evaluate the function of cells that have been given the function of inspection and removal.
3. Future plans
In a culture environment, we will construct multiple intracellular CAs to reflect the will of experts using designed cell-to-cell communication on immune cells or immune cells collected from human or mouse blood, and evaluate their functionality in collaboration with other R&D Items.
In addition, for the safe and secure use of intracellular CA, we will combine multiple intracellular CAs for “stopping” CA-loaded cells based on different principles and evaluate their “forced shutdown” function. For the intracellular CA for forced shutdown, we will evaluate its side-effect effects on cells.