Progress Report
Creating A Society Whose Citizen’s Health is Monitored by Remote Control of Intracellular Cybernetic Avatars[5] Evaluating remote control of intracellular CA in vivo
Progress until FY2024
1. Outline of the project
In this research and development project, we will identify suitable cells to be loaded with intracellular Cybernetic Avatars (hereafter referred to as intracellular CAs), as well as their target cells, and efficiently isolate these selected cells and CA-loaded cells from mouse or human specimens. In collaboration with R&D items 2 to 4, we will work on the design and optimization of intracellular CAs, as well as the development and refinement of techniques for introducing them into cells.
2. Outcome so far
In R&D Item 5, we will establish a highly efficient method for isolating cells targeted for CA (Cybernetic Avatar) integration and CA-loaded cells, in order to enable their generation and functional evaluation (5-1). In collaboration with R&D item 2 to 4, we will evaluate whether the intracellular CA-loaded cells exhibit effective functional controllability — such as detection, elimination, and functional shutdown — toward the target cells (5-2), (5-3) in in vitro settings. Furthermore, we will also conduct in vivo evaluations of the functional controllability of the intracellular CA-loaded cells (5-2), (5-3).
(5-1): We successfully isolated the target cells from a small amount of human samples while maintaining high cell viability, and confirmed that the isolated cells retained their proliferative capacity. Furthermore, to evaluate the function of CA-loaded cells in animal experiments, we collaborated with Section (5-3) to conduct separation tests using small volumes of mouse blood. These tests also confirmed that the target cells could be isolated with high efficiency and viability (Figure 1).
(5-2): We have initiated functional evaluation of intracellular CA by observing the three-way interaction among target cells, inspector cells, and remover cells using a cell dynamics monitoring and sorting platform, as well as single-cell RNA sequencing analysis.
(5-3): We selected immune cells, which can be readily shared and utilized across the project, as the host cells for intracellular CA integration. To enable cooperative elimination of target cells by CA-loaded cells, we designed and constructed the necessary genetic components.
Furthermore in (5-2), (5-3), using a platform for dynamic cell monitoring and separation, we evaluated the functionality of CA-loaded cells and confirmed that CA-loaded effector cells effectively eliminated the target cells (Figure 2).
3. Future plans
We will evaluate whether the engineered CA-loaded cells exhibit the intended functional controllability in response to target cells, using the established experimental system and the platform for dynamic cell monitoring and separation. This evaluation will be conducted in collaboration with other R&D items, and the CA-loaded cells will be refined as needed to achieve more stable functional controllability, with the goal of enabling their functionality within living organisms in the future.