Boolean logic in synthetic biology and biomaterials: Towards living materials in mammalian cell therapeutics

Abstract

Background: The intersection of synthetic biology and biomaterials promises to enhance safety and efficacy in novel therapeutics. Both fields increasingly employ Boolean logic, which allows for specific therapeutic outputs (e.g., drug release, peptide synthesis) in response to inputs such as disease markers or bio‐orthogonal stimuli. Examples include stimuli‐responsive drug delivery devices and logic‐gated chimeric antigen receptor (CAR) T cells. In this review, we explore recent manuscripts highlighting the potential of synthetic biology and biomaterials with Boolean logic to create novel and efficacious living therapeutics. Main body: Collaborations in synthetic biology and biomaterials have led to significant advancements in drug delivery and cell therapy. Borrowing from synthetic biology, researchers have created Boolean‐responsive biomaterials sensitive to multiple inputs including pH, light, enzymes and more to produce functional outputs such as degradation, gel‐sol transition and conformational change. Biomaterials also enhance synthetic biology, particularly CAR T and adoptive T cell therapy, by modulating therapeutic immune cells in vivo. Nanoparticles and hydrogels also enable in situ generation of CAR T cells, which promises to drive down production costs and expand access to these therapies to a larger population. Biomaterials are also used to interface with logic‐gated CAR T cell therapies, creating controllable cellular therapies that enhance safety and efficacy. Finally, designer cells acting as living therapeutic factories benefit from biomaterials that improve biocompatibility and stability in vivo. Conclusion: By using Boolean logic in both cellular therapy and drug delivery devices, researchers have achieved better safety and efficacy outcomes. While early projects show incredible promise, coordination between these fields is ongoing and growing. We expect that these collaborations will continue to grow and realize the next generation of living biomaterial therapeutics.

Multistage Self-Assembled Nanomaterials for Cancer Immunotherapy

“…Due to the programmable delivery and synergistic effect, the selenopeptide nanomedicine achieved a tumor growth inhibition efficacy of 86% in an orthotopic human breast MDA-MB-231 tumor-bearing mouse model, compared with 48% for DOX solely. To make more programmable biomaterials, introducing logic gates into nanomedicine design has attracted much attention [387][388][389]. For instance, Zhang et al induced the concept of logic gates to construct a programmable polymer library [199].…”

“…for DOX solely. To make more programmable biomaterials, introducing logic gates into nanomedicine design has attracted much attention [387][388][389]. For instance, Zhang et al induced the concept of logic gates to construct a programmable polymer library [199].…”

Fluorescein-Based SynNotch Adaptors for Regulating Gene Expression Responses to Diverse Extracellular Cues

“…For example, 'bio-instructive materials' have been developed to mimic natural ECM properties, and such materials have been used to direct the healing and repair of damaged tissues 4,5 . In recent years, tailored biomaterials have also been developed to control engineered cell activities, and these systems have been applied to modulate therapeutic T-cell responses in situ and to facilitate immune cell engineering in vivo [6][7][8][9] . Yet despite these advances, synthetic biology strategies for programming customized ECM-dependent signaling activities have remained relatively limited, especially in comparison to tools for sensing and programming responses to cell-cell interactions [10][11][12][13][14] .…”

3D shape morphing of stimuli-responsive composite hydrogels

“…19 Moreover, the intelligence of these hydrogels goes beyond simple responsive behavior. Advanced smart hydrogels can be programmed to exhibit sequential and logic-gated responses, 20 opening new horizons in the development of active and adaptive materials.…”