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Background of Biologic gate

One area of synthetic biology explores the mechanisms behind the complexity of biological logic gate circuits, aiming to enhance computational speed and unlock biotechnological applications[1].

In electronics, a logic gate is a physical device that implements Boolean functions using input and output signals (0 and 1). Various logic gates are combined to form circuits or devices like multiplexers, registers, arithmetic logic units, and computer memory. These gates are essential for data storage, often arranged in flip-flop circuits, which are fundamental components in digital electronic systems used in computers and communication technologies.

Leveraging principles from electronics, synthetic biologists have designed a variety of biological logic gates. Logic operations are embedded within gene regulatory networks that cells use to process and integrate multiple environmental and cellular signals, allowing them to respond appropriately. By engineering tailored genetic logic circuits that connect various cellular sensors and actuators, we can program living cells to produce specific, desired behaviors in response to particular extracellular or intracellular signaling inputs[2].]

Employing genetic circuits to impart microorganisms with programmable ability, is what we want LANTERN to do —— as an important part of genetic logic circuits, giving complex systems alternative choices when building.

However, many of these gene circuits lack modularity, meaning they are constrained by the need to use specific inputs and outputs[2]. Additionally, they are often not insulated from their host chassis, genetic circuits directly interact with the signals in nature in complex intracellular environments[3].

Given these facts, we consider carefully our LANTERN device.

What can LANTERN do? - SWOT analysis

Strength

Traditional gene circuits are akin to non-programmable components in electronics—once constructed, their logical functions cannot be altered.

The advantages of LANTERN are mainly reflected in the following three aspects:

  • Flexibility: LANTERN can be dynamically adjusted according to specific needs, whereas traditional gene circuits have fixed functions and uses once designed, unable to adapt to environmental or demand changes.
  • Versatility: The complexity and diversity of biological systems necessitate highly flexible control methods. With its dual output, Lantern can perform multiple functions in complex biological environments, whereas traditional gene circuits are notably insufficient in handling complexity and diversity.
  • Precision: Lantern can achieve precise responses to multiple specific conditions, such as precise drug release in smart drug delivery systems, real-time pollutant detection, and treatment in environmental management. LANTERN can simultaneously detect multiple input signals, initiating drug release or pollutant treatment upon meeting certain specific conditions combinations.

Weakness

  • Our genetic circuit could be more manageable and more streamlined due to the combinations of various logic gates;
  • The efficiency, stability, and orthogonality of genetic circuits remained to be enhanced to avoid unwanted crosstalk;
  • Lack of practical application implementation though with rich application prospectives.

Opportunities

  • Enabling memory storage within cells, with effective inheritance passed on to offspring, which could be applied to larger cell factories;
  • Introduced a new concept of "programmable pathway synthetic biology” which shall draw more inspiration from electronic circuits and contribute to the future development of synthetic biology.
  • LANTERN’s high user maneuverability provides clues for personalized medicine, fashion, and so on.

Threat

  • Efficiency and accuracy in practical examination;
  • Others may choose to establish their genetic logic gates from scratch out of concern for the complexity of LANTERN;
  • Non-acceptance of synthetic biology products.

Method of Implementation

Improvement of LANTERN

  • Optimization of Circuit Performance: Iteratively optimize the performance of LANTERN, including input value range, leakage within the circuit, and reducing noise, while also attempting to improve feedback time.
  • Minimization of Cross-Talk: Avoid interference between logic gates and the host organism's environment by using orthogonal systems. Engineering gates with distinct, non-interfering input and output systems ensure minimal cross-talk between different circuits.

Pay attention to other biological gates

  • Diverse Gate Types: Incorporate a variety of logic gates (AND, OR, NOR, NOT, XOR, etc.) into the system to ensure that the genetic circuits can accomplish larger systems.
  • Cross-compatibility with Host Systems: Design similar programmable components across various host biological systems to enhance the component's versatility, laying the foundation for building biological logic circuits.

Safety Consideration

  • Containment Strategies: Implement fail-safe mechanisms to prevent the unintended spread of engineered circuits or gene expression in non-target organisms. We have considered safeguards involving non-natural amino acids, but designing them within this system is quite complex. We hope to find a simpler method for system isolation.
  • Ethical and Regulatory Compliance: Adhere to ethical standards and regulatory guidelines for synthetic biology research and applications, including obtaining approvals from relevant regulatory bodies. Safety assessments and risk evaluations should be conducted thoroughly before large-scale or commercial implementation of biological circuits.

Reference

[1] Singh V. (2014). Recent advances and opportunities in synthetic logic gates engineering in living cells. Systems and synthetic biology, 8(4), 271–282.

[2] Wang, B., Kitney, R., Joly, N. et al. Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology. Nat Commun 2, 508 (2011).

[3] Xia, P., Ling, H., Foo, J. L., & Chang, M. W. (2019). Synthetic genetic circuits for programmable biological functionalities. Biotechnology Advances, 37(6), 107393.