Can Synthetic Biological Products be Applied to the Cartagena Protocol on Biosafety?

Abstract： Synthetic biology has become a formal issue of the Conference of the Parties to the Convention on Biological Diversity（CBD）， but there is no consensus on whether synthetic biological products can be applied to the Cartagena Protocol on Biosafety（the Protocol）. The \"four-level analysis and three-step test\" is proposed to judge the applicable relationship between synthetic biological products and the Protocol. The first level is the living organisms， which is most similar to the living modified organisms （LMOs） defined by the Protocol. It is tested to determine whether it is applicable to the Protocol according to its development stage， the type of product and the technical basis. The second level comprises genetic materials that can be classified as \"living organisms\" through the three-step test， provided they are intended for the generation of biological entities. The third level encompasses biological systems， wherein the living components of these systems can be utilized. The fourth level pertains to the components and products created through synthetic biotechnology. It is generally accepted that components and products generated via DNA sequencing technology do not need to undergo this classification process. Components and products based on DNA synthesis techniques， genome design， synthesis and assembly， and gene editing techniques can be judged by reference to the material level analysis method. For the components and products generated by component engineering and circuit engineering， if they are composed of biological elements and gene circuits to generate higher-level biological systems and have the possibility of generating biological entities， the Protocol can be applied.

Keywords： synthetic biology products; the Biosafety Protocol; modified living organisms; synthetic biology

CLC： D 99 " " " " DC： A " " " " " " Article： 2096?9783（2024）03?0139?10

1 Introduction

In October 2021， the first phase of the fifteenth meeting of the Conference of the Parties to the Convention on Biological Diversity（CBD） adopted the \"Kunming Declaration\" in China， which commits to strengthen measures and their implementation for the development， assessment， regulation， management and transfer of relevant biotechnology to enhance benefits and reduce risks， including those associated with the use and release of the living modified organisms（LMOs） that may have adverse environmental impacts[1]. At the same time， the Conference also adopted the Kunming-Montreal Global Biodiversity Framework， with building， strengthening and implementing capacity for biosafety measures as one of the specific action objectives. Synthetic biology is the new development of modern life science and biotechnology， which is the frontier representative of original breakthrough and interdisciplinary integration in the field of biology in the 21st century. It has made remarkable achievements in many fields such as bioenergy， biomaterials， medical technology and exploration of life laws[2]. It is of great significance to solve global problems such as biodiversity loss， environmental pollution， climate change and food crisis. In September 2022， the United States promulgated the National Biotechnology and Biomanufacturing Program， which regards synthetic biology as an important technology to maintain the strength of bioeconomy and emphasizes that the program will give priority to investment in biosafety research[3]. Concerns surrounding the biosafety governance implications of synthetic biology have garnered increasing attention.

As an important international convention for the protection and utilization of global biological resources， the CBD discussed synthetic biology as a formal issue at the Twelfth Meeting of the Conference of the Parties held in Pyeongchang， South Korea， as early as October 2014. The Cartagena Protocol on Biosafety （the Protocol） is an important extension of the Convention in the field of biosafety governance， which focuses on the transboundary movement， transit， handling and use of all LMOs obtained by modern biotechnology that may have adverse effects on the conservation and sustainable use of biological diversity[4]. It emphasizes a precautionary approach to ensuring the biosafety of all LMOs through an early informed consent procedure. Synthetic biology has the characteristics of convergence， subversion and strategic science. The synthetic biological products produced under the guidance of the concepts of building knowledge and buildings for use are more complex and uncertain. Its biosafety governance is of great significance.

The Conference of the Parties to the CBD maintains a high degree of attention to the adverse effects of the development of synthetic biology， and has repeatedly called for the identification of the relationship between any synthetic biology product and LMOs （as defined in the Protocol）. Such as the twelfth meeting of the Conference of the Parties to the CBD[5]， the 20th meeting of the Subsidiary Body on Scientific， Technical and Technological Advice（the SBSTTA）[6-7]， etc. In addition， in December 2020， the Executive Secretary of the 24th meeting of the SBSTTA requested Parties to submit information on newly developed living organisms in synthetic biology that may exceed the scope of LMOs defined in the Protocol， and to hold a forum on synthetic biology for thematic discussions[8]. Many researchers have also provided opinions on this. David Leary questioned the extent to which some of the assertions and conclusions of these papers are actually justified by reference to analysis of the existing law[9]. Synthetic biology relies mainly on digital genetic sequences， rather than tangible biological molecules. And it was applied by the Protocol， because it applies only to physical biological material[10]. "Sonia Allan also thought synthetic biology could lead to gaps in the risk assessment framework of the Protocol， since it may not be capable of dealing with complex hybrids of genetic material（including some that are wholly synthetic in design and origin） and the properties and effects they display[11]. Oldham Hall and Burton He emphasized six key issues worthy of further study， to solve to what extent both the CBD and the Protocol apply to synthetic biology[12]. At the same time， Brendan Parent thinks synthetic biology organism is a category of Living Modified Organisms， but the Protocol's efficacy in protecting against synthetic biology hazards is questionable[13]. Article 4 of the Protocol stipulates that the applicable object is the LMOs. Therefore， whether synthetic biological products belong to the LMOs is the premise of whether they can be applied. Most of the existing studies have discussed whether synthetic biology should be applied to the Protocol， but have not proposed specific steps on how to judge the relationship between synthetic biological products and LMOs.

This paper first reviews the progress of negotiations on synthetic biology by the Conference of the Parties to the CBD， and then puts forward specific judgment steps （the four-level analysis and three-step test） to clearly judge the relationship between synthetic biological products and LMOs， which clarify whether synthetic biological products can be applied to the Protocol under the framework of the CBD.

2 Progress in the Negotiation of Synthetic Biology under the Framework of the CBD

The Protocol is a legally binding instrument based on the relevant provisions and principles of the CBD and the Rio Declaration on Environment and Development to regulate the biosafety issues caused by the transboundary movement of all LMOs. With the discussion of synthetic biology as a New amp; Emerging the Conference of the Parties， the safety issues brought by synthetic biology have gradually attracted the attention of the Conference of the Parties to the CBD.

The understanding of synthetic biology by the Conference of the Parties to the CBD is achieved through the recommendations of the SBSTTA and the decisions of the Conference of the Parties. The \"Newamp; Emerging Issues\" is issues related to biodiversity conservation and sustainable use proposed by the Executive Secretary at the Conference of the Parties to the CBD based on the proposals of the Parties and adopted by the SBSTTA[14]. With the rapid development of modern biotechnology， the Canadian Institute for Environmental Law and Policy submitted a proposal for nanotechnology， biotechnology and genetically modified organisms to the scientific advisory body in July 2008. Subsequently， Parties and relevant organizations have repeatedly submitted proposals to the SBSTTA on synthetic biology as a New amp; Emerging Issues related to the conservation and sustainable use of biodiversity （Table 1）， and the urgency and importance of synthetic biology as a formal topic of the CBD have become increasingly prominent.

Between April 2012 and December 2020， the SBSTTA issued five recommendations regarding the development of synthetic biology （Table 2）， "consistently maintaining a cautious stance towards its advancement. On the one hand， they affirmed the benefits of the development of synthetic biology for biodiversity and human health. On the other hand， it is hoped that synthetic biology can be included in the scope of supervision of the CBD and the Protocol. At the same time， it is noted that scientific uncertainties in synthetic biology led it to maintain a conservative attitude as to whether living organisms resulting from applications in synthetic biology were modified as defined in the Protocol.

The recommendations of the SBSTTA on synthetic biology have been valued by the Conference of the Parties to the CBD， and four consecutive Conferences of the Parties have taken decisions on synthetic biology since 2012（Table 3）. The Conference of the Parties has reached a consensus on the potential benefits and adverse effects of the definition and development of synthetic biology on the objectives of the CBD， the Protocol and the Nagoya Protocol. However， there are still doubts about whether the synthetic biological products are consistent with the LMOs， and the AHTEG on synthetic biology is required to continue its research.

When the Protocol was first drafted， a clear distinction was made between the scopes of organisms. With the development of biotechnology， the distinction of organisms has become increasingly difficult and ambiguous. If the Protocol's definition of \"modern biotechnology\" was strictly applied to take into account the need for overcoming \"natural physiological or reproductive or recombination barriers and that are not techniques used in traditional breeding and selection\"， some recombinant DNA （e.g.， cisgenesis） and \"new\" technologies （e.g.， genome editing or synthetic biology） may be excluded from its scope[21]. It is important to assess whether synthetic biological products align with the definition of LMOs under the CBD framework. However， it is even more crucial to analyze the potential biosafety risks posed by synthetic biological products， based on the Convention's definition of synthetic biology， and to introduce specific methods for regulating the application of synthetic biological products under the Protocol.

3 Application of Synthetic Biological Products under the Rules of the Biosafety Protocol

There are three levels of understanding of the applicable relationship between the Protocol and synthetic biological products. The first is whether the Protocol should be applied to synthetic biological products. The second is whether the Protocol has the potential to apply to synthetic biological products， and the last is the analysis steps of synthetic biological products applicable to the Protocol. Given that the Conference of the Parties to the CBD has already reached consensus and made decisions regarding the first and two issues， this paper will not delve into an analysis of those matters. Judging the relationship between synthetic biological products and the LMOs defined by the Protocol is the key to figuring out how to apply them. According to the decision of the Conference of the Parties to the CBD on synthetic biology[24]， synthetic biological products include genetic materials， living organisms， and biological systems. Combined with the content identified by the AHTEG on Synthetic Biology requested by the Twelfth Meeting of the Conference of the Parties to the CBD， the \"four-level analysis and three-step test\" is proposed for whether synthetic biological products are applicable to the Protocol.

3.1 The First Level： Whether \"Living Organisms\" is Applicable to the Protocol

The living organisms in synthetic biological products are most similar to the LMOs， but the Conference of the Parties to the CBD has recognized that there are different gaps between synthetic biological products and the LMOs in different stages of development[24]. Therefore， the application of synthetic biological products in different stages of development and application differs.

3.1.1 The First Step is to Test from the Perspective of the Stage of Synthetic Biological Products

In the early stage， the research and application of synthetic biology may produce both living organisms and non-living organisms， such as proteins， and primitive cells[26]. If the initially generated object is a living organism， it resembles a modified living organism and poses a biosafety risk. Therefore， the Protocol can be directly applied. Consequently， the second step of the assessment would involve evaluating the object from the perspective of synthetic biology product types. If the object initially generated is a non-organism （e.g. Virus-like macromolecular components）， it cannot apply the Protocol. Although there is an overlap in the techniques used， the non-organism is essentially different in nature from the LMOs and generally does not pose a biosafety risk. In the later stage of Ramp;D and application， the technical certainty of synthetic biological products is greatly improved. Similar to the LMOs， it can be applied to the Protocol and enter the second step of analysis.

3.1.2 The Second Step is to Test from the Perspective of Synthetic Biology Product Types

The essence of the LMOs defined by the Protocol is a living biological entity， including non-reproducing organisms， viruses and viroids. From the perspective of living organisms， if a synthetic biological product is a living organism， it is similar to the LMOs and the Protocol may be applied. At this time， the third step is to judge from the perspective of technical basis. If the synthetic biology product is not a living organism， for example， a material based on semiconductor synthetic biology[27]， it does not pose a biosafety risk. Therefore， the Protocol is not applicable. From the perspective of reproduction， if a synthetic biology product is a reproductive organism， it is not similar to LMOs and cannot be subject to the Protocol. However， if it is a non-reproductive organism entity， it is similar to LMOs and can be assessed under the Protocol. In this case， the product would proceed to the third step of the evaluation process.

3.1.3 The Third Step is to Test the Technical Basis of Synthetic Biological Products

Article 3 of the Protocol stipulates that the technical basis for obtaining the LMOs is modern biotechnology， which specifically refers to two types of biotechnology， namely， in vitro nucleic acid techniques and fusion of cells beyond the taxonomic family. In addition， the technical basis of synthetic biological products also includes gene editing technology， gene element and gene recombination technology. Synthetic biological products， which based on in vitro nucleic acid techniques and fusion of cells beyond the taxonomic family， are similar to modified living organisms therefore the Protocol can be applied.

Gene editing technology is the application of the phenomenon of DNA breakage and its repair mechanism[28]. It has four main repair mechanisms， classical non-homologous end joining （NHEJ）， alternative end joining （a-EJ）， single-strand annealing （SSA） and homologous recombination （HR）[29]. The techniques in vitro nucleic acid is mainly a combination or application of DNA， so gene editing technology is a more basic biotechnology. If the synthetic biological products based on gene editing technology also involve the assembly and application of organism DNA level， it can also be applied to the Protocol. On the contrary， it should be analyzed as a genetic material.

Gene recombination technology refers to the use of recombinant DNA tools to recombine deoxyribonucleic acid （DNA） molecules in vitro according to people's wishes， and then introduce recombinant molecules into recipient cells and make them proliferate in corresponding cells[30]. The synthetic biological products produced by this technology are similar to the LMOs produced by in vitro nucleic acid techniques， and the Protocol can be applied.

3.2 The Second Level： Whether \"Genetic Material\" is Applicable to the Protocol

Genetic material is a DNA fragment containing genetic information[31]， which is one of the important foundations of organisms， and a more microscopic expression of living organisms. Living organisms under the framework of the CBD refer to biological entity that can transfer or replicate genetic materials. Genetic materials are similar to that of living organisms[4].

If the genetic material has no possibility of subsequent generation of biological entity， it does not apply the Protocol. However， if the genetic material is an infectious genetic material that may cause harm to humans， animals or plants， it may pose a biosafety risk. So it can be applied to the Laboratory Biosafety Manual （4th Edition） developed by the World Health Organization[32].

If the purpose of genetic material is to generate biological entity， it can be considered to be included in the category of \"living organisms\" for judgment. When they escape or overwhelm their intended environment， self-replicating re-engineered cells may produce undesired consequences[33]. Genetic material， like the cells， will also self-replicate. For the transboundary movement， transit， handling and use of genetic materials， the \"three-step test\" method should be used for specific analysis.

3.3 The Third Level： Whether \"Biological System\" is Applicable to the Protocol

Biological system is a huge complex system， which is independent of non-biological systems. It has the characteristics of integrity， correlation and self-organization[34]. The concept of a biological system is broader than that of a living organism， as it examines and studies organisms and the biological world from a systems theory perspective， emphasizing their functional and instrumental attributes. For example， Science reported a general chemical synthesis system based on artificial intelligence automation in 2020. A powerful synthetic biotechnology is formed by intelligent analysis of chemical synthesis literature to form synthetic process information and synthesis of target chemicals through digital and automated execution systems， including genetic substances or proteins[35]. Biological systems are different from genetic substances or living organisms. They do not point to a specific biological entity alone， but the integration of independent biological subsystems from micro to macro. Therefore， as far as the biological system is concerned， there is no need to apply the Protocol.

The biological system is hierarchical， which is characterized by the relative stability of each subsystem from sub-cellular cell tissue， to population and community. Each subsystem has unique properties and functions. Therefore， the biological subsystems that constitute biological entity within the biological system are similar to the LMOs and can be applied to the Protocol. For those biological subsystems at the level of non-biological entity which are significantly different from the LMOs， the Protocol cannot be applied.

3.4 The Fourth Level： Whether \"Components and Products Generated by Synthetic Biotechnology\" is Applicable to the Protocol

The twelfth meeting of the Conference of the Parties to the CBD， requires the AHTEG on synthetic biology to identify the relationship between the LMOs and organisms， components and products based on synthetic biotechnology. The previous analysis method can be used for the organism part， but it is necessary to analyze the components and products generated by synthetic biotechnology separately. Synthetic biology is an excellent enabling technology[36]， which includes DNA sequencing technology， DNA synthesis technology， genome design， synthesis and assembly， gene editing technology， element engineering （including new protein design）， circuit engineering， computing and modeling[37].

Whether the components and products generated by the above technologies are applicable to the Protocol needs to be classified and discussed. "Components and products derived from DNA sequencing technology， which is primarily focused on identifying and expressing genetic information， generally do not pose significant biosafety risks or impact the objectives of the Protocol and the CBD. Therefore， the application of the Biosafety Protocol is typically not necessary for these types of synthetic biology developments. The components and products generated by DNA synthesis technology， genome design， synthesis and assembly， and gene editing technology， due to the technical objects are mostly related to genetic materials， can be judged by referring to the analysis method at the level of genetic materials to ensure whether it applies to the Protocol.

The components and products generated by component engineering and loop engineering cannot apply to the Protocol. Because the biological element is the smallest unit of the whole biological system， it is far from the biological entity. However， the combination of biological elements and gene circuits to generate higher-level biological systems， which can form biological entity or have the potential to form it. Therefore， the Protocol can be applied to those components and products. At the same time， some of the components and products generated based on the synthetic gene circuit are not biological entity parts， such as bladder cancer gene diagnosis and treatment products based on synthetic gene circuits[38]. These components and products are not similar to the LMOs， therefore they cannot be applied to the Protocol.

4 Conclusion

Synthetic biology opens up a new world full of possibilities， challenges and controversies， with unlimited opportunities and huge biosafety risks. Although the Conference of the Parties to the CBD has reached a consensus on the scientific scope of synthetic biology， not all synthetic biological products can be applied to the Protocol. The \"four-level analysis and three-step test\" based on the scientific connotation of synthetic biology is proposed under the framework of the CBD， as an analytical method to ensure whether synthetic biological products are applicable to the Protocol. The \"four-level analysis\" is to analyze the differences with the LMOs from four levels： living organisms， genetic materials， biological systems， components and products generated by synthetic biotechnology. The \"three-step test\" is a three-step test of the application of the Protocol from the development stage of synthetic biological products， the types of products and the technical basis of synthetic biological products. Clarifying the applicable relationship between synthetic biological products and the Protocol is the first step to strengthen the biosafety governance of synthetic biology under the framework of the CBD， and it is also an important basis for promoting the safety and sustainable development of synthetic biology. The biosafety management of synthetic biological products must start from the linkage， trans-nationality and diversity of biosafety issues， uphold the concept of global safety management based on consultation， co-construction and sharing， strengthen international cooperation and dialogue， actively participate in the formulation of international rules for the safety management of synthetic biology， and provide and continuously optimize the plan for the global biosafety management system.

References：

[1] MINISTRY OF ECOLOGY AND ENVIRONMENT THE PEOPLE'S REPUBLIC OF CHINA， the COP15 high-level meeting adopted the \"Kunming Declaration\"[EB/OL]. [2024-03-25]. https：//www.mee.gov.cn/ywdt/hjywnews/202110/t20211013_956425.shtml.

[2] DENG Z X. Synthetic biology takes advantage of the best era， building knowledge and building for use[J]. Chinese Bulletin of Life Sciences， 2019， 31（4）： 323?324.

[3] FACT SHEET. President Biden to Launch a National Biotechnology and Biomanufacturing Initiative[EB/OL]. [2024-03-25]. https：//www.presidency.ucsb.edu/documents/fact-sheet-president-biden-launch-national-biotechnology-and-biomanu?facturing-initiative.

[4] CBD （Convention on Biological Diversity）， Text of the Cartagena Protocol on Biosafety[EB/OL]. [2024-03-25].http：//bch.cbd.int/protocol/text/.

[5] CBD （Convention on Biological Diversity）， COP 12 Decisions Twelfth meeting of the Conference of the Parties to the Convention on Biological Diversity： Decision XII/24 'DECISION ADOPTED BY THE CONFERENCE OF THE PARTIES TO THE CONVENTION ON BIOLOGICAL DIVERSITY'[EB/OL]. [2024-03-25]. https：//www.cbd.int/doc/decisions/cop-12/cop-12-dec-24-en.pdf.

[6] CBD （Convention on Biological Diversity）， Subsidiary Body on Scientific， Technical and Technological Advice （SBSTTA） Introduction[EB/OL]. [2024-03-25]. https：//www.cbd.int/sbstta/.

[7] CBD （Convention on Biological Diversity）， Twentieth meeting of the Subsidiary Body on Scientific， Technical and Technological Advice： Recommendation SBSTTA-XX/8[EB/OL]. [2024-03-25]. https：//www.cbd.int/doc/recommendations/sbstta-20/sbstta-20-rec-08-en.pdf.

[8] CBD （Convention on Biological Diversity）， Open-Ended Forum， Topic 5： Consider whether any living organism developed thus far through new developments in synthetic biology fall outside the definition of living modified organisms as per the Cartagena Protocol[EB/OL]. [2024-03-25]. https：//bch.cbd.int/synbio/open-ended/discussion_2019?2020/？threadid=9602.

[9] LEARY D. The synthetic biology revolution： mapping a future research agenda[J]. University of Tasmania Law Review， 2015， 34（1）： 111?127.

[10] AKPOVIRI F， ZAINOL Z A， BAHARUM S N. Synthetic biology and biosafety governance in the European Union and the United States[J]. IIUM Law Journal， 2020， 28（1）： 69.

[11] ALLAN S. Report on macquarie university workshop on ethical， legal and social Issues raised by synthetic biology[J]. Macquarie Law Journal， 2015（15）： 5?26.

[12] OLDHAM P， HALL S， BURTON G. Synthetic biology： mapping the scientific landscape[J]. PLoS Clinical Trials， 2012， 7（4）： 12?14.

[13] PARENT. Reproduction-powered industry： coordinating agency regulations for synthetic biology[J]. North Carolina Journal of Law amp; Technology， 2013， 15（2）： 307?357.

[14] QIU M H， HUANG Y， ZHANG J Q， et al. International negotiations on synthetic biology and China's implementation strategies within the Convention on Biological Diversity framework[J]. Biodiversity Science， 2016（1）： 114?120.

[15] EcoNexus， founded in February 2000， is a small public interest research organization consisting of scientists and dedicated researchers analyzing and reporting on new technologies that have the potential for significant negative impacts on biodiversity and ecosystems[EB/OL]. [2024-03-25]. https：//www.econexus.info/about-econexus.

[16] CBD （Convention on Biological Diversity）， Meeting Documents： Sixteenth meeting of the Subsidiary Body on Scientific， Technical and Technological Advice[EB/OL]. [2024-03-25]. https：//www.cbd.int/meetings/SBSTTA-16.

[17] CBD （Convention on Biological Diversity）， Meeting Documents： Eighteenth meeting of the Subsidiary Body on Scientific， Technical and Technological Advice[EB/OL]. [2024-03-25]. https：//www.cbd.int/meetings/SBSTTA-18.

[18] CBD （Convention on Biological Diversity）， Meeting Documents： Twentieth meeting of the Subsidiary Body on Scientific， Technical and Technological Advice[EB/OL]. [2024-03-25]. https：//www.cbd.int/meetings/SBSTTA-20.

[19] CBD （Convention on Biological Diversity）， Meeting Documents： Twenty-second meeting of the Subsidiary Body on Scientific， Technical and Technological Advice[EB/OL]. [2024-03-25]. https：//www.cbd.int/meetings/SBSTTA-22.

[20] CBD （Convention on Biological Diversity）， Meeting Documents： Twenty-fourth meeting of the Subsidiary Body on Scientific， Technical and Technological Advice[EB/OL]. [2024-03-25]. https：//www.cbd.int/meetings/SBSTTA-24.

[21] KEIPER F， ATANASSOVA A. Regulation of synthetic biology： developments under the convention on biological diversity and its protocols[J]. Frontiers in bioengineering and biotechnology， 2020（8）： 1?20.

[22] CBD （Convention on Biological Diversity）， DECISION ADOPTED BY THE CONFERENCE OF THE PARTIES TO THE CONVENTION ON BIOLOGICAL DIVERSITY AT ITS ELEVENTH MEETING[EB/OL]. [2024-03-25]. https：//www.cbd.int/decisions/cop/？m=cop-11.

[23] CBD （Convention on Biological Diversity）， DECISION ADOPTED BY THE CONFERENCE OF THE PARTIES TO THE CONVENTION ON BIOLOGICAL DIVERSITY[EB/OL]. [2024-03-25]. https：//www.cbd.int/doc/decisions/cop-12/cop-12-dec-24-en.pdf.

[24] CBD （Convention on Biological Diversity）， DECISION ADOPTED BY THE CONFERENCE OF THE PARTIES TO THE CONVENTION ONBIOLOGICAL DIVERSITY[EB/OL]. [2024-03-25]. https：//www.cbd.int/doc/decisions/cop-13/cop-13-dec-17-en.pdf.

[25] CBD （Convention on Biological Diversity）， DECISION ADOPTED BY THE CONFERENCE OF THE PARTIES TO THE CONVENTION ON BIOLOGICAL DIVERSITY[EB/OL]. [2024-03-25]. https：//www.cbd.int/doc/decisions/cop-14/cop-14-dec-19-en.pdf.

[26] CBD （Convention on Biological Diversity）， CONSIDERATIONS ON SYNTHETIC BIOLOGY AS PER DECISION 14/19[EB/OL]. [2024-03-25]. https：//www.cbd.int/doc/c/ce25/cb28/e5146103f15a131dd39103f0/synbio-ahteg-2019-01-02-en.pdf.

[27] WANG X， ZHAO P. Research advances in semiconductor synthetic biology[J]. CIESC Journal， 2021， 72（5）： 2426?2435.

[28] LU J N， CHU X. "Advances and challenges in gene editing technologies[J]. Bulletin of Chinese Academy of Sciences， 2018， 33（11）： 1184?1192.

[29] HOWARD H， CHANG Y， NICHOLAS R P， et al. Non-homologous DNA end joining and alternative pathways to double-strand break repair[J]. Nature Reviews Molecular Cell Biology， 2017，18（8）： 495?506.

[30] YANG J， DENG Y. Key technologies and applications of synthetic biology[J]. Biotechnology Bulletin， 2017， 33（1）： 12?23.

[31] ZHANG X L. On gene rights[J]. Law Review， 2010， 28（3）： 88?92.

[32] World Health Organization， Laboratory biosafety manual， 4th edition[EB/OL]. [2024-03-25]. https：//www.who.int/publications/i/item/9789240011311.

[33] WRIGHT O ， STAN G B ， ELLIST. Building-in biosafety for synthetic biology[J]. Microbiology （Reading， England）， 2013，159： 1221?1235.

[34] WU X J， LI A M. The modern biology study must be guided by systematic perspective[J]. Journal of Biology， 2019， 36（1）： 126?129.

[35] MEHR S， HESSAM M， MATTHEW C， et al. A universal system for digitization and automatic execution of the chemical synthesis literature[J]. Science， 2020， 370（6512）： 101?108.

[36] LI L， JIANG W H. Recent advances in the enabling technologies for synthetic biology[J]. Scientia Sinica（Vitae）， 2015， 45（10）： 950?968.

[37] ZHANG X N. Synthetic biology in China： review and prospects[J]. Scientia Sinica（Vitae）， 2019， 49（12）： 543?1572.

[38] LIU Y， ZENG Y， LIU L， et al. Synthesizing and gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells[J]. Nature Communications， 2014，5（5）： 1?7.

合成生物學(xué)生成物能否適用于《卡塔赫納生物安全議定書》？

邵 " 濱1，喻 " 玲1，焦洪濤2

（1. 湖南大學(xué) "法學(xué)院，長沙 "410082；2. 華中科技大學(xué) "法學(xué)院，武漢 430074）

摘 " "要：合成生物學(xué)已成為《生物多樣性公約》（以下簡稱《公約》）締約方大會的重要談判議題，但合成生物學(xué)生成物能否適用《卡塔赫納生物安全議定書》（以下簡稱《議定書》）卻尚未達成共識。在《公約》框架下提出“四層次分析+三步檢驗法”作為判斷合成生物學(xué)生成物與《議定書》適用關(guān)系的方法：第一層次是活性生物體，與《議定書》界定的改性活生物體最相似，根據(jù)其所處發(fā)展階段、生成物種類和所依賴的技術(shù)基礎(chǔ)三步進行檢驗，以判斷其是否適用《議定書》。第二層次是基因物質(zhì)，如果其以生成生物實體為目的，那么可以將其納入“活性生物體”范疇考慮，運用三步檢驗法進行具體分析。第三層次是生物系統(tǒng)，生物系統(tǒng)中的生物活體部分，可以適用《議定書》。第四層次是由合成生物技術(shù)生成的組成部分和產(chǎn)品，由DNA測序技術(shù)生成的組成部分和產(chǎn)品無需適用《議定書》；基于DNA合成技術(shù)、基因組設(shè)計、合成與組裝、基因編輯技術(shù)生成的組成部分和產(chǎn)品，可以參照因物質(zhì)層次的分析方法進行判斷；基于元件工程、回路工程生成的組成部分和產(chǎn)品，由生物元件與基因回路組成后生成更高層級的生物系統(tǒng)且具有生成生物實體可能的部分，可以適用《議定書》。

關(guān)鍵詞：合成生物學(xué)生成物；《生物安全議定書》；改性活生物體；合成生物學(xué)