In this section we discuss GIFTs (Gate-controlled Internal Flawless systems) from the perspective of ELSI—ethical, legal, and social issues. While advances in science and technology have generated substantial benefits to society, they have also, at times, posed significant social and environmental challenges. Therefore, the development and implementation of emerging technologies must be accompanied by prior assessments of their potential impacts from an ELSI perspective. Researchers and stakeholders thus share the responsibility of envisioning a sustainable future, which requires inclusive dialogue among experts and diverse communities.

The civilian and military applications of emerging technologies are often inseparable, producing what is known as the “dual-use dilemma.” While GIFTs offer promising applications—such as precision drug delivery, molecular robotics, and synthetic cell engineering—they could, in principle, be misappropriated for harmful purposes, including targeted delivery of toxins or bioweapons.

Molecular robot-like GIFTs equipped with DNA nanostructures may also be perceived as “quasi-intelligent” entities responsive to environmental stimuli. This raises concerns about unintended or uncontrolled behaviors that could generate social risks. Although the immediate threat of misuse remains limited due to the nascent stage of the technology, the potential for malicious exploitation may increase as design flexibility expands and implementation progresses. Accordingly, transparency, rigorous ethical review, principles of safe design, and adherence to the framework of Responsible Research and Innovation (RRI) are imperative from the earliest stages of development.

The future implementation of GIFT-based technologies highlights significant regulatory challenges. In medical applications, such as drug delivery, the incorporation of multiple therapeutics within a single liposome may complicate classification under existing regulatory frameworks, such as the Pharmaceuticals and Medical Devices (PMD) Act. Furthermore, inadequate control of nanostructure stability or degradability could lead to body retention or environmental dispersal, warranting regulatory oversight.

Although the present study does not involve genetic modification or genome editing, the DNA origami scaffold strand (M13mp18) contains viral genetic sequences. It is employed solely as a structural element, without transcription or translation. Thus, the research does not fall under the scope of the Cartagena Act or related international treaties. Nevertheless, DNA usage as genetic engineering may lead to public misunderstanding, necessitating proactive dissemination of accurate information and educational initiatives to prevent misconceptions and unwarranted conflict.

Liability in the event of malfunction represents another legal challenge. For instance, if a GIFT-based nanorobot malfunctions in vivo, the attribution of responsibility—whether to the developer, manufacturer, or medical practitioner—would be legally complex. To address such issues, legal and regulatory frameworks must clarify the distribution of responsibility and obligations across both direct and indirect stakeholders. In the longer term, harmonization of national regulations with international standards will be essential to ensure safety, accountability, and public trust.

The synthesis of GIFTs employs cholesterol-modified DNA, albeit in minute quantities that pose no known health risks. Nevertheless, given the public association of cholesterol with cardiovascular disease, misperceptions are possible. Additionally, chloroform—used in lipid preparation—is a volatile, toxic, and carcinogenic substance. However, proper handling under fume hoods can ensure product safety. The use of benign solutes such as glucose and trehalose further enhances biocompatibility.

Despite these safeguards, the safety of GIFTs manufactured outside controlled laboratory conditions cannot be guaranteed. Thus, establishing standardized safe materials, preparation methods, and transparent communication of safety protocols is crucial. Such measures are indispensable for ensuring accountability and fostering societal trust in the technology.