基因组转座子挖掘及其应用

主要开展转座子介导基因传递技术、基因编辑技术、分子标记技术研发及其应用研究，研究方向包括：（1）转座子进化、活性DNA转座子挖掘及高效基因传递工具开发; （2）转座子起源小分子靶向核酸酶挖掘及基因编辑工具开发；（3）大片段DNA定点整合技术研发；（4）逆转座子插入多态RIP分子标记规模挖掘及配套芯片研发。研究主要使用大肠杆菌、 哺乳动物细胞、酵母细胞、斑马鱼、小鼠和猪模型生物等。

1. 转座子进化及其生物学意义

转座子的转座特性使其能够水平传播，颠覆了人们对生命演化过程中关于遗传物质垂直传播的传统认识。这一特征使遗传物质能够在不同的物种、界和域之间发生水平转移。解析转座子的起源、分类、横向传播、驯化（蛋白编码基因驯化）和适应（基因拼接元件和表达调控调节元件，如增强子、启动子、lncRNA等）等进化规律，揭示转座对重塑功能基因、基因组、转录组和表观组中的作用，对理解转座子在功能基因演化、基因组进化、表型变异和物种分化中的生物学功能有重要意义。

2. 活性转座子挖掘及高效基因传递工具开发

转座子的转座特性使其具有介导大片段DNA转移的能力，挖掘活性转座子，进行高效基因传递工具开发和工程化优化，在人类基因治疗和转基因生物育种中有广泛应用前景。

Fig.1. Structure of cut-and-paste transposons and their transposition mechanism. (A) The transposon is a mobile genetic element containing a transposase coding sequence (green box) flanked by terminal inverted repeats (TIRs; orange arrows on the left and right). (B) The transposase (green spheres) binds to its sites within the transposon TIRs (orange boxes). Excision takes place in a synaptic complex, and separates the transposon from the donor DNA (gray box). The excised element integrates into a target site in the target DNA (yellow box). This process generates target site duplications (TSDs, black boxes) which flank the newly integrated transposon. Most cut-and-paste transposons generate a transposon excision footprint in the donor DNA.

Fig.2. Experimental pipeline for the development of genetic tools based on active DNA transposons.

3. 转座子起源小分子靶向核酸酶挖掘及基因编辑工具开发

目前基因编辑中广泛应用的Cas9和Cas12a（Cpf1）核酸酶分子比较大（1200-1400 aa），给系统遗传改造、基因包装和细胞传递带来诸多不便，且基因编辑效率还不高，存在脱靶现象，严重制约了CRISPR/Cas技术在基因治疗、生物育种等领域的应用。

TnpB 是一种与转座子相关的小分子靶向核酸酶，研究表明三类转座子（IS605, IS607, IS1341）含有TnpB。它是 RNA引导的核酸酶，在细菌和古菌中广泛存在。近年来，TnpB 因其与 CRISPR-Cas 系统的相似性而受到关注，被认为是 CRISPR-Cas 系统的进化前体之一。TnpB能够加工自身的mRNA以产生引导RNA。这些引导RNA是短RNA分子，能够将TnpB核酸酶引导到特定的DNA序列。加工过程涉及对mRNA的切割，生成引导RNA，随后引导RNA用于将核酸酶活性定位到基因组中的正确位置

小分子靶向核酸酶具有许多优点，如易于合成、稳定性高，便于遗传修饰和细胞传递等。通过对原核生物基因组大数据挖掘转座子起源的小分子核酸酶，并利用人工智能（AI）等技术，进行定向进化、分子重构，研发基因编辑效率高、靶向特异性强的新型基因编辑工具，能够为人类基因治疗和转基因生物育种提供更加安全高效的编辑系统。

4. 大片段DNA定点整合技术研发

逆转录转录病毒和DNA转座子作为基因传递系统已经有大量的研究报道。然而逆转录病毒依靠内源性逆转录酶活性以及通过复制粘贴机制进行转座。 且由于涉及RNA中间体和逆转录，逆转录病毒介导的转基因可能不稳定。另外，逆转录病毒载体制备和储存比较复杂、载体容量有限、生物安全要求高、成本高昂。

相比之下，DNA转座子利用简单的“剪切粘贴”机制，其介导的基因传递相对简单且转基因片段更加稳定。科学家已经成功挖掘并改造了多种DNA转座子（如ZB、PS、SB和piggyBac），作为高效的基因传递载体，用于基因治疗，转基因和突变体制备。与逆转录病毒载体相比，DNA转座子作为基因治疗传递载体具有成本低廉、载体容量大、整合稳定、易于操作，受免疫系统沉默的影响小等优点。

然而，由于在基因组上的随机整合，目前基于DNA转座子载体（包括逆转录病毒载体）传递系统的基因治疗技术仍然存在一些潜在风险，如随机整合导致基因突变，致癌基因的激活或肿瘤抑制基因的失活等，这些可能会导致肿瘤的形成，这种现象被称为插入突变，以上风险是目前逆转录病毒载体和DNA转座子载体在基因治疗中主要安全性关切和挑战。

因此，靶向转座DNA转座子挖掘，并利用人工智能（AI）等技术的后续工程化改造，开发高效的基因定点转移技术，可以大大降低由随机整合引起的风险，显著提高DNA转座子介导基因治疗的安全性。

另外，通过转座酶和小分子靶向核酸酶融合，构建大片段DNA定点整合技术也是实验室重点攻关方向。

5. 基于活性转座子插入多态为基础的分子标记研发及其在动物遗传育种研究中的应用

由于转座子能在物种间和物种内转移，因此，像其它的突变源一样，能够产生丰富的基因组结构变异，转座产生的结构变异也称为转座子插入多态。转座子是很多模式动物基因组主要成份，占斑马鱼基因组55%左右，蛙类基因组35%左右，家蚕基因组45%左右，逆转录转座子（Retrotransposon）占哺乳动物基因组30-50% ，占家猪基因组40%左右，是哺乳动物基因组主要成分，主要分为长散在重复序列（LINEs）、短散在重复序列（SINEs）和长末端重复序列（LTRs，含内源性逆转录病毒，ERVs）三种类型。

由于转座子插入片段大（一般100 bp以上），且大多含有功能元件（启动子、增强子等），转座产生的结构变异产生的遗传效应普遍比SNP更强。转座插入能够通过导入调控元件、改变基因拼接方式、改变表观调控等方式引起基因功能和活性改变，从而引起表型变异。另外，由于转座产生的结构变异是由内源性转座酶介导，而SNP是自然突变，其突变率（2.5×10⁻²）比SNP（1.0-1.8×10^–8）高。

转座子的转座不仅促进了物种间基因组的分化，而且还产生了物种内丰富的遗传多样性，对物种、品种、亚种、品系和新性状形成发挥了重要作用。因此，转座子插入形成的多态是重要的新型分子标记，其在遗传进化研究中的应用为我们理解高等生物基因组的进化提供了全新视角，同时，转座子插入多态分子标记技术也成为生物多样性、遗传进化和分子育种研究的重要工具。

与传统SNP标记相比，转座子插入多态分子标记具有突变率高、稳定性好、数量大、分布范围广、遗传效应大、检测手段简单快速和开发成本低等特点。因此，基于基因组上转座子插入多态的分子标记规模挖掘及其配套芯片研发在QTL精细定位、全基因组选择等遗传育种研究中具有更高的应用价值。

猪等家畜基因组中50%以上的结构变异由逆转座子介导产生（也称为逆转座子插入多态RIP，Retrotransposon Insertion Polymorphism），特别SINE逆转座子（家畜基因组上分布最广泛，多态最丰富的一类转座子）产生的RIP标记最具开发潜力。

转座子实验室主要研究方向为基因组转座子挖掘及其应用，主要开展转座子介导基因传递技术、基因编辑技术、分子标记技术研发其应用研究，包括：（1）转座子进化、活性DNA转座子挖掘及高效基因传递工具开发; （2）转座子起源小分子靶向核酸酶挖掘及基因编辑工具开发；（3）大片段DNA定点整合技术研发；（4）逆转座子插入多态RIP分子标记规模挖掘及配套芯片研发。研究主要使用大肠杆菌（E.Coli）、 哺乳动物细胞、酵母细胞、斑马鱼、小鼠和猪模型生物等。实验室现有教授2人，副教授1人，助理研究员1人，博士后1人，博硕士研究生20余人。    

宋成义，博士、教授，博士研究生导师

研究兴趣：转座组与基因组共进化、转座子介导基因转移、基因编辑、分子标记技术研发其应用研究。

1.学习经历
1993-1997	攻读学士学位（畜牧专业）	江苏农学院
1997-2000	攻读硕士学位（动物遗传育种与繁殖专业）	扬州大学
2006-2010	攻读博士学位（动物遗传育种与繁殖专业）	扬州大学
2.工作简历
2014.08-至今	扬州大学	教授
2018.02-2018.05	德国Leibniz家畜研究所基因组研究所 Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Rostock, Germany	访问学者
2014.09-2015.09	英国伯明翰大学肿瘤和基因组研究所 Institute of Cancer and Genomic Sciences University of Birmingham, Birmingham, UK	博士后
2010.08-2014.08	中国农业科学院北京畜牧兽医研究所	博士后
2008.08-2014.07	扬州大学	副教授
2006.09-2007.09	德国卡尔斯鲁厄理工学院遗传病毒所 （原卡尔斯鲁厄研究中心） Institute of Toxicology and Genetics Karlsruhe Institute of Technology (Formerly Forschungszentrum Karlsruhe), Karlsruhe, Germany	访问学者
2002.08-2008.07	扬州大学	讲师
2000.07-2002.07	扬州大学	助教

扬州大学教师个人主页服务平台 宋成义–中文主页–首页 (yzu.edu.cn)

ORCID: https://orcid.org/0000-0002-0488-4718

高波，博士，教授，博士研究生导师

主要从事基因组一类逆转座子 （Retrotransposon）、二类（DNA transposon）转座子，靶向转座子系统和基因编辑系统挖掘及其在转基因和基因治疗研究中的应用研究。

ORCID: Bo Gao (0000-0002-4029-1258) (orcid.org)

王宵燕、博士、副教授、硕士研究生导师

研究方向：1、猪的重要经济性状遗传机理解析；2、猪的常规育种与分子育种；3、猪遗传资源评价与保护；4、猪健康养殖。

ORCID: 0000-0001-8521-2974

陈才、博士、助理研究员、硕士研究生导师

主要研究方向和兴趣：1、基于活性转座子插入多态为基础的分子标记研发及其在动物遗传育种研究中的应用；2、动物转座组和基因组共进化研究（包括转座子分布、适应、驯化、横向传播及其对基因和基因组进化的影响）。 

扬州大学教师个人主页服务平台 陈才–中文主页–首页 (yzu.edu.cn)

王赛赛、博士后、助理研究员

主要研究方向和兴趣：活性转座子的研发，主要通过生物信息学的方法挖掘自主活性的DNA转座子，并研究该转座系统的活性及转座特性；转座子技术在转基因和动物功能基因学上的应用研究。

2013年河北科技师范学院动物科学专业毕业；
2015年扬州大学养殖专业硕士毕业；
2021年扬州大学动物遗传育种与繁殖专业博士毕业；

Ahmed Abdelkader Saleh 博士后

Education: Graduated from Alexandria University, Egypt. Majoring in Biological Science. Postgraduate studies in Animal Genetics and Breeding, Alexandria University, Egypt. Obtained an MSc degree in Molecular Markers from Alexandria University and City of Scientific Research & Technology Applications, Egypt. Ph.D. degree in Animal Genetics and Breeding, Southwest University (SWU), China. Postdoctoral research in Animal Genetics, Alexandria University, Egypt. MSc in Human Development, Diplomatic Training Centre, Egypt. BMA in Business Administration, Egyptian Cultural Centre, Egypt.
Research direction & Interest: Previously focused on animal genetics and breeding especially ”farm animals”. Areas of scientific interest include; candidate genes also their association with production and reproductive traits, MAS, signatures of selection, QTL, GWAS, GEBV, besides, the biodiversity of AnGR. Current research interests have a strong emphasis on Bioinformatics, DNA & RNA transposons mainly in animal genomes and their applications as genetic tools. Our research includes animal genome transposon identifications, classification, and evolution. Also, we mining for highly active transposons and testing their activities in human cells.
Positions: Serves as a faculty member (Assistant Professor) at the lab of animal Genetics and Breeding, Alexandria University, Egypt. Serves as an Arbitrator in the International Arbitration Organization. Consultant Trainer at Diplomatic Training Centre. Researcher at the City of Scientific Research and Technology Applications. Postdoctoral researcher at Yangzhou University, China.

在读博士研究生

Mohamed Diaby博士，2018-2022

Education: Graduated from AL-AZHAR University (Egypt), majoring in Animal Production. Postgraduate studies in animal physiology, Cairo University (Egypt). MSc degree in Sustainable Agriculture (Animal Production), a joint degree from Chiang Mai University (Thailand) and University of Hohenheim (Germany).

Research direction and interest: I am engaged in DNA transposon mainly in the animal genomes and their applications as genetic tools. Our research includes animal genome transposon identification, classification, and evolution. Also, I am mining for high active DNA transposons and testing their activities in the human cells.

Numan Ullah博士, 2018-2022

Numan heals from Northern Pakistan with an Undergraduate and Master’s degree from Peshawar, Pakistan. He joined Yangzhou University in the fall of 2018. His PhD research involves characterizing new CRISPR-Cas systems and improving their efficiency by developing fusion proteins. He is interested in developing improved gene-editing systems and their application in gene therapy.

杨乃苏博士，2018-2022

2016年扬州大学动物科学专业毕业，擅长功能基因组学分析和生物信息数据挖掘，目前主要从事基因组转座子挖掘及其应用研究。

ALI SHOAIB ALI ABDALLAH博士，2020-2024

Ali Shoaib Moawad from Egypt with an undergraduate and master’s degree from Kafrelsheikh University, Egypt. He works as Assistant Lecturer, Animal Production Department, Faculty of Agriculture, Kafrelsheikh University, Egypt. He joined Yangzhou University in the fall of 2020. His PhD research includes Retrotransposons annotation and evolution in the genome of livestock.

郑尧博士，2021-2025

2016年江苏畜牧兽医职业技术学院专科毕业；2017年扬州大学动物科学与技术学院毕业；2021年扬州大学畜牧学专业硕士毕业；目前博士研究生阶段就读于扬州大学畜牧学专业，主要研究的方向是扬大BBY小型猪培育和RNA转座子插入位点对基因、基因组以及表型的影响。对于SINE、LINE、ERV不同类型的RNA转座子分类，本人目前主要对SINE转座子作为研究对象，借助比较基因组学的方法，进行生物信息学的分析并挖掘猪全基因组水平的SINE转座子多态插入位点，同时根据插入位点的坐标分析，探究SINE转座子与靶基因、lncRNA之间的互作关系，从而揭示SINE转座子对插入多态对基因、基因组以及表型存在重要的影响。

石莎莎博士，2022-2026

2015.09-2019.06就读于河南科技大学动物科学与技术学院，专业：动物科学；2019年-至今就读于扬州大学动物科学与技术学院，专业：畜牧学；主要研究方向：DNA转座子的挖掘及应用，主要包括（1）转座子鉴定、分类、进化、注释等研究；（2）高活性DNA 转座子的挖掘、验证及转座子技术在转基因中的应用。

Asare Emmanuel博士，2022-2026

Graduated from Animal Science in 2021, with a master’s degree in Animal Husbandry in 2021. Currently studying for a Doctorate Degree in Animal Genetics, Breeding and Reproduction

在读硕士研究生

Addy George

何佳硕士，2021-2024

2021年扬州大学动物科学专业毕业，目前动物遗传育种与繁殖专业硕士在读，主要研究影响猪生长发育的重要反转座子分子标记，为研发与应用反转座子标记提供依据。

郭梦可硕士，2021-2024

2021年河南牧业经济学院动物科学专业毕业，目前动物遗传育种与繁殖专业硕士在读，主要研究CRISPR/Cas系统同源蛋白的挖掘与开发。

王冰清硕士 ，2022-2025

2022年扬州大学本科毕业，主要研究动物基因组转座子，包括转座子的挖掘、鉴定、分类、进化分析以及活性转座子开发、优化与应用。

向奎琳硕士 ，2022-2025

2022年扬州大学本科毕业，目前动物遗传育种与繁殖专业硕士在读，主要从事转座子鉴定、分类、进化、注释以及高活性DNA转座子的挖掘、验证。

于淼硕士，2022-2025

女，辽宁鞍山，满族。2022年沈阳工学院动物科学专业毕业，现就读于扬州大学畜牧专业硕士，主要研究猪的反转座子插入多态挖掘。

周辰宇，2023-2026

周辰宇，男，江苏泰州，2023年于扬州大学动物科学专业本科毕业，现就读于扬州大学畜牧学动物遗传与育种方向学术型硕士，主要研究方向为猪的反转座子插入多态验证与挖掘

王全，2023-2026

2023年扬州大学动物科学专业毕业，现就读于扬州大学畜牧学硕士，主要从事高活性DNA转座子的挖掘和活性验证。

陈红，2023-2026

2023年扬州大学本科毕业，现就读于扬州大学畜牧学专业，主要从事转座子鉴定、分类、进化、注释以及高活性转座子的挖掘、验证。

客座研究生

肖迎港博士，2023-2027

肖迎港，男，四川成都，汉族。2020年遵义医科大学麻醉学专业毕业，2023年扬州大学麻醉学硕士毕业，目前扬州大学麻醉学学术型博士在读，主要研究方向和兴趣：全身静脉麻醉药毒性；斑马鱼胚胎生长发育；转座子介导的认知功能障碍；生物信息学。

袁文娟硕士，2021-2024

2021年新乡医学院麻醉学专业毕业，目前扬州大学麻醉学学术型硕士在读，主要研究全身麻醉药物对斑马鱼胚胎发育的影响、斑马鱼药物筛选模型。

毕业博士研究生

王亚丽博士，2018-2022 2014年石河子大学动物科学专业毕业，2016年动物遗传育种与繁殖专业硕士毕业，主要研究方向为精准基因编辑工具优化和挖掘。

杜站宇博士，2019-2023 2013年白城师范学院生物技术专业毕业，2017年吉林农业大学生物化学与分子生物学专业硕士毕业，2019年就读于扬州大学畜牧学专业，全日制博士。主要研究方向和兴趣：猪基因组；反转座子结构解析；基因结构变异；哺乳动物毛色相关研究；生物信息学。

陈才，2015-2019

研究方向和兴趣：1、基于活性转座子插入多态为基础的分子标记研发及其在动物遗传育种研究中的应用；2、动物转座组和基因组共进化研究（包括转座子分布、适应、驯化、横向传播及其对基因和基因组进化的影响）。    

沈丹，2016-2020

2013年扬州大学动物科学专业，2016年扬州大学动物遗传育种与繁殖专业硕士毕业，2020年扬州大学动物遗传育种与繁殖专业博士毕业。主要的研究方向是以斑马鱼和小鼠为研究对象，开展DNA转座子的挖掘与应用研究工作。研究生期间，在导师宋成义教授的指导下成功挖掘到了一个斑马鱼（ZeBrafish）的活性转座子，并将其命名为ZB转座子。ZB转座子不仅在宿主斑马鱼体内有较高的转座活性，而且在哺乳动物中也具备较高跳跃的能力，因此可作为高效的遗传研究工具被广泛应用。此外，ZB转座子现已获得国家发明专利授权。

王赛赛，2017-2021

2013年河北科技师范学院动物科学专业毕业；

2015年扬州大学养殖专业硕士毕业；

2021年扬州大学动物遗传育种与繁殖专业博士毕业；

主要研究方向和兴趣：活性转座子的研发，主要通过生物信息学的方法挖掘自主活性的DNA转座子，并研究该转座系统的活性及转座特性；转座子技术在转基因和动物功能基因学上的应用研究。

毕业硕士研究生

关中夏硕士，2019-2022 2019年毕业于扬州大学动物科学与技术学院，目前主要研究方向为DNA转座子的挖掘与转座子介导载体的构建。

迟诚林硕士，2019-2022 2018年山东畜牧兽医职业技术学院专科毕业；2019年扬州大学动物科学与技术学院毕业；2022年扬州大学畜牧学专业硕士毕业。主要研究的方向是基于活性转座子插入多态为基础的分子标记研发及其在动物遗传育种研究中的应用。

贾文竹硕士，2020-2023 2020年扬州大学动物科学专业毕业，现就读于扬州大学畜牧学专业，主要研究方向是转座子的挖掘与改造，希望转座子被更多地应用到医学等领域，发挥潜能与优势。

王梦礼硕士，2020-2023女，河南洛阳，汉族。2016.09-2020.06就读于河南牧业经济学院动物科技学院，专业：动物科学；2020年-至今就读于扬州大学动物科学与技术学院，专业：畜牧学；现阶段进行‘基于结构变异鉴定策略的猪全基因组SINE逆转座子插入多态（RIP）标记开发’的研究。

Tn as non-viral vectors in immunetherapy

PiggyBac

A first-in-human clinical trial of piggyBac transposon-mediated GMR CAR-T cells against CD116-positive acute myeloid leukemia and juvenile myelomonocytic leukemia]. Rinsho Ketsueki. 2022https://doi.org/10.11406/rinketsu.63.776

A new approach to CAR T-cell gene engineering and cultivation using piggyBac transposon in the presence of IL-4, IL-7 and IL-21. Cytotherapy. 2018 https://doi.org/10.1016/j.jcyt.2017.10.001

Applications of piggyBac Transposons for Genome Manipulation in Stem Cells. Stem Cells Int. 2021https://doi.org/10.1155/2021/3829286

Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. Cytotherapy. 2014 https://doi.org/10.1016/j.jcyt.2014.05.022

Antileukemic potency of CD19-specific T cells against chemoresistant pediatric acute lymphoblastic leukemia. Exp Hematol. 2015https://doi.org/10.1016/j.exphem.2015.08.006

Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34(+) cells of juvenile myelomonocytic leukemia. J Hematol Oncol. 2016 https://doi.org/10.1186/s13045-016-0256-3

Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice. Cell Death Dis. 2018https://doi.org/10.1038/s41419-017-0238-6

Autologous antigen-presenting cells efficiently expand piggyBac transposon CAR-T cells with predominant memory phenotype. Mol Ther Methods Clin Dev. 2021https://doi.org/10.1016/j.omtm.2021.03.011

Autologous non-human primate model for safety assessment of piggyBac transposon-mediated chimeric antigen receptor T cells on granulocyte-macrophage colony-stimulating factor receptor. Clin Transl Immunology. 2020https://doi.org/10.1002/cti2.1207

CAR T Cell Generation by piggyBac Transposition from Linear Doggybone DNA Vectors Requires Transposon DNA-Flanking Regions. Mol Ther Methods Clin Dev. 2020https://doi.org/10.1016/j.omtm.2019.12.020

Characterizing piggyBat-a transposase for genetic modification of T cells. Mol Ther Methods Clin Dev. 2022 Mar 22;25:250-263.https://doi.org/10.1016/j.omtm.2022.03.012

Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma. Mol Ther Oncolytics. 2021 https://doi.org/10.1016/j.omto.2021.03.001

Development of CAR T-cell lymphoma in 2 of 10 patients effectively treated with piggyBac-modified CD19 CAR T cells. Blood. 2021https://doi.org/10.1182/blood.2021010813

Differences in the phenotypes and transcriptomic signatures of chimeric antigen receptor T lymphocytes manufactured via electroporation or lentiviral transfection. Front Immunol. 2023https://doi.org/10.3389/fimmu.2023.1068625

Direct Delivery of piggyBac CD19 CAR T Cells Has Potent Anti-tumor Activity against ALL Cells in CNS in a Xenograft Mouse Model. Mol Ther Oncolytics. 2020https://doi.org/10.1016/j.omto.2020.05.013

EGFRvIII-specific CAR-T cells produced by piggyBac transposon exhibit efficient growth suppression against hepatocellular carcinoma. Int J Med Sci. 2020https://doi.org/10.7150/ijms.45603

Engineered CAR T cells targeting mesothelin by piggyBac transposon system for the treatment of pancreatic cancer. Cell Immunol. 2018 https://doi.org/10.1016/j.cellimm.2018.04.007

Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor in piggyBac Transposon-Engineered T Cells. Mol Ther Methods Clin Dev. 2017https://doi.org/10.1016/j.omtm.2017.12.003

Enzymatically produced piggyBac transposon vectors for efficient non-viral manufacturing of CD19-specific CAR T cells. Mol Ther Methods Clin Dev. 2021https://doi.org/10.1016/j.omtm.2021.08.006

Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19⁺ Tumor Cells. Front Immunol. 2022https://doi.org/10.3389/fimmu.2021.802705

Evaluation of piggyBac-mediated anti-CD19 CAR-T cells after ex vivo expansion with aAPCs or magnetic beads. J Cell Mol Med. 2021https://doi.org/10.1111/jcmm.16118

Inducible secretion of IL-21 augments anti-tumor activity of piggyBac-manufactured chimeric antigen receptor T cells. Cytotherapy. 2020 https://doi.org/10.1016/j.jcyt.2020.08.005

Integration Mapping of piggyBac-Mediated CD19 Chimeric Antigen Receptor T Cells Analyzed by Novel Tagmentation-Assisted PCR. EBioMedicine. 2018https://doi.org/10.1016/j.ebiom.2018.07.008

Investigation of product-derived lymphoma following infusion of piggyBac-modified CD19 chimeric antigen receptor T cells. Blood. 2021https://doi.org/10.1182/blood.2021010858

In Vivo Piggybac-Based Gene Delivery towards Murine Pancreatic Parenchyma Confers Sustained Expression of Gene of Interest. Int J Mol Sci. 2019https://doi.org/10.3390/ijms20133116

Low-cost generation of Good Manufacturing Practice-grade CD19-specific chimeric antigen receptor-expressing T cells using piggyBac gene transfer and patient-derived materials. Cytotherapy. 2015 Sep;17(9):1251-67.https://doi.org/10.1016/j.jcyt.2015.05.013

Manufacturing NKG2D CAR-T cells with piggyBac transposon vectors and K562 artificial antigen-presenting cells. Mol Ther Methods Clin Dev. 2021 https://doi.org/10.1016/j.omtm.2021.02.023

piggyBac-Based Non-Viral In Vivo Gene Delivery Useful for Production of Genetically Modified Animals and Organs. Pharmaceutics. 2020 https://doi.org/10.3390/pharmaceutics12030277

piggyBac-transposon-mediated CAR-T cells for the treatment of hematological and solid malignancies. Int J Clin Oncol 28, 736–747 (2023). https://doi.org/10.1007/s10147-023-02319-9

PiggyBac-Engineered T Cells Expressing CD19-Specific CARs that Lack IgG1 Fc Spacers Have Potent Activity against B-ALL Xenografts. Mol Ther. 2018https://doi.org/10.1016/j.ymthe.2018.05.007

PiggyBac-engineered T cells expressing a glypican-3-specific chimeric antigen receptor show potent activities against hepatocellular carcinoma. Immunobiology. 2020https://doi.org/10.1016/j.imbio.2019.09.009

 PiggyBac-modified CD19-expressing 4T1 cell line for the evaluation of CAR construct. Int J Clin Exp Pathol. 2019https://pubmed.ncbi.nlm.nih.gov/31934091

PiggyBac-engineered T cells expressing a glypican-3-specific chimeric antigen receptor show potent activities against hepatocellular carcinoma. Immunobiology. 2020https://doi.org/10.1016/j.imbio.2019.09.009

PiggyBac-Engineered T Cells Expressing CD19-Specific CARs that Lack IgG1 Fc Spacers Have Potent Activity against B-ALL Xenografts. Mol Ther. 2018 https://doi.org/10.1016/j.ymthe.2018.05.007

PiggyBac transposon system with polymeric gene carrier transfected into human T cells. Am J Transl Res. 2019http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6895516/

PiggyBac Transposon-Mediated CD19 Chimeric Antigen Receptor-T Cells Derived From CD45RA-Positive Peripheral Blood Mononuclear Cells Possess Potent and Sustained Antileukemic Function. Front Immunol. 2022https://doi.org/10.3389/fimmu.2022.770132

PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report. Front Immunol. 2021 https://doi.org/10.3389/fimmu.2021.599493

Phase I clinical trial of EGFR-specific CAR-T cells generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer patients. J Cancer Res Clin Oncol. 2021 https://doi.org/10.1007/s00432-021-03613-7

Quantum pBac: An effective, high-capacity piggyBac-based gene integration vector system for unlocking gene therapy potential. FASEB J. 2023https://doi.org/10.1096/fj.202201654r

Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using PiggyBac: A case report. Front Immunol. 2022 Dec 1;13:1007210.https://doi.org/10.3389/fimmu.2022.1007210

Safety and Efficacy of an Immune Cell-Specific Chimeric Promoter in Regulating Anti-PD-1 Antibody Expression in CAR T Cells. Mol Ther Methods Clin Dev. 2020https://doi.org/10.1016/j.omtm.2020.08.008

Two cases of T cell lymphoma following Piggybac-mediated CAR T cell therapy. Mol Ther. 2021 https://doi.org/10.1016/j.ymthe.2021.08.013

Sleeping Beauty 

AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells. Nat. Biomed. Eng (2023).https://doi.org/10.1038/s41551-023-01058-6

Targeted delivery of a PD-1-blocking scFv by CD133-specific CAR-T cells using nonviral Sleeping Beauty transposition shows enhanced antitumour efficacy for advanced hepatocellular carcinoma. BMC Med. 2023https://doi.org/10.1186/s12916-023-03016-0

Sleeping Beauty kit sets provide rapid and accessible generation of artificial antigen-presenting cells for natural killer cell expansion. Immunol Cell Biol. 2023https://doi.org/10.1111/imcb.12679

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Front Immunol. 2022https://doi.org/10.3389/fimmu.2022.1032397

Generation of CAR-T Cells with Sleeping Beauty Transposon Gene Transfer. Methods Mol Biol. 2022https://doi.org/10.1007/978-1-0716-2441-8_3

Minicircles for CAR T Cell Production by Sleeping Beauty Transposition: A Technological Overview. Methods Mol Biol. 2022https://doi.org/10.1007/978-1-0716-2441-8_2

CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma. Gene Ther. 2021https://doi.org/10.1038/s41434-021-00254-w

 Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities. J Clin Invest. 2020 https://doi.org/10.1172/jci138473

 Optimisation of Tet-On inducible systems for Sleeping Beauty-based chimeric antigen receptor (CAR) applications. Sci Rep. 2020 https://doi.org/10.1038/s41598-020-70022-0

Targeting CD33 in Chemoresistant AML Patient-Derived Xenografts by CAR-CIK Cells Modified with an Improved SB Transposon System. Mol Ther. 2020 https://doi.org/10.1016/j.ymthe.2020.05.021

Long-term outcomes of Sleeping Beauty-generated CD19-specific CAR T-cell therapy for relapsed-refractory B-cell lymphomas. Blood. 2020https://doi.org/10.1182/blood.2019002920

Generation of CAR+ T Lymphocytes Using the Sleeping Beauty Transposon System. Methods Mol Biol. 2020https://doi.org/10.1007/978-1-0716-0146-4_9

Shortened ex vivo manufacturing time of EGFRvIII-specific chimeric antigen receptor (CAR) T cells reduces immune exhaustion and enhances antiglioma therapeutic function. J Neurooncol. 2019 https://doi.org/10.1007/s11060-019-03311-y

Universal allogeneic CAR T cells engineered with Sleeping Beauty transposons and CRISPR-CAS9 for cancer immunotherapy. Mol Ther. 2022https://doi.org/10.1016/j.ymthe.2022.06.006

Enhanced Biosafety of the Sleeping Beauty Transposon System by Using mRNA as Source of Transposase to Efficiently and Stably Transfect Retinal Pigment Epithelial Cells. Biomolecules. 2023https://doi.org/10.3390/biom13040658

A highly soluble Sleeping Beauty transposase improves control of gene insertion. Nat Biotechnol. 2019 https://doi.org/10.1038/s41587-019-0291-z

CAR T Cells Generated Using Sleeping Beauty Transposon Vectors and Expanded with an EBV-Transformed Lymphoblastoid Cell Line Display Antitumor Activity In Vitro and In Vivo. Hum Gene Ther. 2019https://doi.org/10.1089/hum.2018.218

Preclinical Efficacy and Safety of CD19CAR Cytokine-Induced Killer Cells Transfected with Sleeping Beauty Transposon for the Treatment of Acute Lymphoblastic Leukemia. Hum Gene Ther. 2018https://doi.org/10.1089/hum.2017.207

Antitumor activity of CD56-chimeric antigen receptor T cells in neuroblastoma and SCLC models. Oncogene. 2018https://doi.org/10.1038/s41388-018-0187-2

Minicircle-Based Engineering of Chimeric Antigen Receptor (CAR) T Cells. Recent Results Cancer Res. 2016https://doi.org/10.1007/978-3-319-42934-2_3

Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors. PLoS One. 2016https://doi.org/10.1371/journal.pone.0159477

Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition from minicircle vectors. Leukemia. 2017https://doi.org/10.1038/leu.2016.180

Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016 https://doi.org/10.1172/jci86721

Sleeping Beauty Transposition of Chimeric Antigen Receptors Targeting Receptor Tyrosine Kinase-Like Orphan Receptor-1 (ROR1) into Diverse Memory T-Cell Populations. PLoS One. 2015https://doi.org/10.1371/journal.pone.0128151

Manufacture of T cells using the Sleeping Beauty system to enforce expression of a CD19-specific chimeric antigen receptor. Cancer Gene Ther. 2015https://doi.org/10.1038/cgt.2014.69

A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19. Immunol Rev. 2014https://doi.org/10.1111/imr.12137

 Clinical application of Sleeping Beauty and artificial antigen presenting cells to genetically modify T cells from peripheral and umbilical cord blood. J Vis Exp. 2013https://doi.org/10.3791/50070

 Sleeping beauty system to redirect T-cell specificity for human applications. J Immunother. 2013https://doi.org/10.1097/cji.0b013e3182811ce9

The hyperactive Sleeping Beauty transposase SB100X improves the genetic modification of T cells to express a chimeric antigen receptor. Gene Ther. 2011https://doi.org/10.1038/gt.2011.40

Gene Therapy with the Sleeping Beauty Transposon System. Trends Genet. 2017https://doi.org/10.1016/j.tig.2017.08.008

 Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform. Oncotarget. 2016https://doi.org/10.18632/oncotarget.9955

Transgene Expression and Transposition Efficiency of Two-Component Sleeping Beauty Transposon Vector Systems Utilizing Plasmid or mRNA Encoding the Transposase. Mol Biotechnol. 2023 https://doi.org/10.1007/s12033-022-00642-6

Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications of Sleeping Beauty, piggyBac and Tol2 for Genome Engineering. Int J Mol Sci. 2021 https://doi.org/10.3390/ijms22105084

Non-Viral Engineering of CAR-NK and CAR-T cells using the Tc Buster Transposon System™https://doi.org/10.1101/2021.08.02.454772

Tc Buster Transposon Engineered CLL-1 CAR-NK Cells Efficiently Target Acute Myeloid Leukemia, blood, 2023 https://doi.org/10.1182/blood-2021-147244

The Tol2 transposon system mediates the genetic engineering of T-cells with CD19-specific chimeric antigen receptors for B-cell malignancies. Gene Ther. 2015 Feb;22(2):209-15.https://doi.org/10.1038/gt.2014.104

Non-viral chimeric antigen receptor (CAR) T cells going viral. Immunooncol Technol. 2023 Mar 9;18:100375. https://doi.org/10.1016/j.iotech.2023.100375

Progress of Transposon Vector System for Production of Recombinant Therapeutic Proteins in Mammalian Cells. Front Bioeng Biotechnol. 2022https://doi.org/10.3389/fbioe.2022.879222

Improving cell and gene therapy safety and performance using next-generation Nanoplasmid vectors. Mol Ther Nucleic Acids. 2023 Apr 7;32:494-503. https://doi.org/10.1016/j.omtn.2023.04.003

Preclinical and clinical advances in transposon-based gene therapy. Biosci Rep. 2017https://doi.org/10.1042/bsr20160614

 Transposon-mediated gene transfer into adult and induced pluripotent stem cells. Curr Gene Ther. 201https://doi.org/10.2174/156652311797415836

Nonviral genome engineering of natural killer cells. Stem Cell Res Ther. 2021https://doi.org/10.1186/s13287-021-02406-6

Potential of transposon-mediated cellular reprogramming towards cell-based therapies. World J Stem Cells. 2020https://doi.org/10.4252/wjsc.v12.i7.527

Non-Viral Gene Delivery Systems. Pharmaceutics. 2021https://doi.org/10.3390/pharmaceutics13040446

Immune cell therapies, CAR-T/CAR-NK

Challenges and new technologies in adoptive cell therapy. J Hematol Oncol. 2023https://doi.org/10.1186/s13045-023-01492-8

CAR T therapy beyond cancer: the evolution of a living drug. Nature. 2023 Jul;619(7971):707-715. https://doi.org/10.1038/s41586-023-06243-w

Bridging live-cell imaging and next-generation cancer treatment. Nat Rev Cancer. 2023https://doi.org/10.1038/s41568-023-00610-5

CAR T-Cell Production Using Nonviral Approaches. J Immunol Res. 2021 https://doi.org/10.1155/2021/6644685

Overhauling CAR T Cells to Improve Efficacy, Safety and Cost. Cancers (Basel). 2020https://doi.org/10.3390/cancers12092360

Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy. Front Immunol. 2023 May 2;14:1166038. https://doi.org/10.3389/fimmu.2023.1166038

Improving cell and gene therapy safety and performance using next-generation Nanoplasmid vectors. Mol Ther Nucleic Acids. 2023 Apr 7;32:494-503.https://doi.org/10.1016/j.omtn.2023.04.003

Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells. Front Immunol. 2023 Mar 6;14:1121030.https://doi.org/10.3389/fimmu.2023.1121030

CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies. Front Immunol. 2023 Feb 20;14:1101495.https://doi.org/10.3389/fimmu.2023.1101495

2022

Automated, scaled, transposon-based production of CAR T cells. J Immunother Cancer. 2022 Sep;10(9):e005189.http://dx.doi.org/10.1136/jitc-2022-005189

The Past, Present, and Future of Non-Viral CAR T Cells. Front Immunol. 2022 Jun 9;13:867013. https://doi.org/10.3389/fimmu.2022.867013

The future of engineered immune cell therapies. Science. 2022 Nov 25;378(6622):853-858. https://doi.org/10.1126/science.abq6990

CAR-T cells leave the comfort zone: current and future applications beyond cancer. Immunother Adv. 2020https://doi.org/10.1093/immadv/ltaa006

Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies. Stem Cell Res Ther. 2022https://doi.org/10.1186/s13287-022-03163-w

Transposons: Moving Forward from Preclinical Studies to Clinical Trials. Hum Gene Ther. 2017https://doi.org/10.1089/hum.2017.128

Chimeric antigen receptor-natural killer cells: a promising sword against insidious tumor cells. Hum Cell. 2023https://doi.org/10.1007/s13577-023-00948-w

Engineering CAR-NK cells: how to tune innate killer cells for cancer immunotherapy. Immunother Adv. 2022https://doi.org/10.1093/immadv/ltac003

TE keynote lectures

*Part 1: Introduction to transposable elements (38 minutes) by Susan Wessler

*Part 2: How transposable elements amplify throughout genomes (70 minutes) by Susan Wessler

*Transposable Element-mediated Structural Variation: From McClintock to Pangenomes – YouTube by Susan Wessler, department of Botany and Plant Sciences, University of California (55 minutes)

The Dynamic Genome: Unintelligent Design – YouTube by Susan Wessler department of Botany and Plant Sciences, University of California (60 minutes)

LINE1 by Haig Kazazian Jr – YouTube 43′

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ZFIN The Zebrafish Information Network

DANIO-CODE programme (birmingham.ac.uk)

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一、转座元件 介绍

TE education: RepBase (girinst.org)

转座元件（Transposable element，TE）

转座元件（Transposable element，简称TE），又称转座子或移动元件，是一类DNA片段的集合，可以通过转座作用在基因组中从一个位置移动或复制到另一个位置。TE的长度范围从小于100个碱基对到超过20,000个碱基对不等。转座之后，很多类型TE两侧都含有短的（约1-20个碱基对）直接重复序列，这些直接重复序列是转座过程中从靶序列中衍生出来的靶位点重复序列（target site duplications，TSDs)。然而，一些TE类型，例如Helitron、几个Harbinger家族和CR1逆转座子，不产生TSDs。TSD的长度通常是一组TE及其相关物种的特征，但在不同家族和超家族中可能有所变化。在多数真核生物基因组中，TE是重复序列的主要成份。其他重复序列包括串联重复序列（卫星序列或微卫星）、零星的基因组重复以及一些多拷贝宿主基因（如rRNA、tRNA、组蛋白基因等）。事实上，TE可以被视为基因组内的寄生元件。同样地，细胞间病毒也可以被视为TE，因为它们可以整合到宿主基因组中，例如LTR-逆转录病毒。TE对宿主基因组具有多样化的进化影响。

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Transposable element – Wikipedia

转座元件

转座元件（TE），也称为转座子或跳跃基因，是DNA中的一种核酸序列，可以在基因组内改变其位置，有时会介导产生突变或逆转突变，从而改变细胞的遗传特征和基因组大小。转座往往导致相同遗传物质的复制。在人类基因组中，L1和Alu转座子是两个典型例子。巴巴拉·麦克林托克在1983年因发现转座子而获得了诺贝尔奖。 转座子在个性化医学中的重要性日益凸显；在多维大数据组学分析中，转座子也越来越受到关注。

在真核生物中，转座子占据了基因组的很大一部分，是真核细胞中DNA质量的主要决定因素。尽管转座子是自私的遗传元件，但许多转座子在基因组功能和进化中都发挥重要作用。转座子对于科学研究人员来说也非常有用，可以利用转座子对活有机体进行体内DNA遗传修饰。

转座子至少可以分为两大类：I类转座子（也称逆转录转座子），通常需要通过逆转录方式介导转座，而II类转座子（也称DNA转座子），能编码转座酶，介导转座（包括转座子在原有位置的切除和和新位置的插入），有些转座子也编码其他蛋白质。

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Copy-out–Paste-in IS elements identifed in prokaryotes

Families	groups	Size-range	DR	Ends	IRs	Nb ORF	Frameshift	Chemistry
IS1	IS1	740-1180	8-9	GGnnnTG	Y	2	ORFAB	DDE
	ISMhu11	900-4600	0-10		Y	2	ORFAB
IS3	IS911	1250			Y	2	ORFAB
	IS150	1200-1600	3-4	TG	Y	2	ORFAB	DDE
	IS407	1100-1400	4	TG
	IS51	1000-1400	3-4	TG
	IS3	1150-1750	3-4	TGa/g
	IS2	1300-1400	5	TG
IS481	–	950-1300	4-15	TGT	Y	1
IS30	–	1000-1700	2-3		Y	1		DDE
IS110	IS110	1200-1550	0		N			DEDD
	IS1111				Y *			DEDD
IS256	–	1200-1500	8-9	Ga/g	Y	1		DDE
ISL3	–	1300-2300	8	GG	Y	1
IS21	–	1750-2600	4-8	TG	Y	2 *		DDE
ISLre2

Classification, terminal features, TSD features and the number of entries of DNA transposons in Repbase

Eukaryotic cut-and-paste transposase superfamilies

Fig. 2. An unrooted consensus tree of the transposase superfamilies inferred from the presence or absence of the highly conserved residues in the signature strings. Bootstrap values are at the nodes. The arrows with labels indicate superfamily clusters merged in our revised classification. Shown on the right is a schematic representation of the DDE/D domain and the signature string for each superfamily. Conserved blocks are highlighted in blue, variable regions are in gray. White gaps are regions not drawn to scale. The DDE triads are highlighted in red. Alternative residues are marked by slashes; lowercase indicates that a residue occurs in <10% of the sequences in the alignment profile. The C/DH motif is highlighted in orange; the C(2)C, [M/L]H, and H(3-4)H motifs are highlighted in green.

List of Copy-out–Paste-in IS elements

List of mobile elements whose transposases have been examined by secondary structure prediction programs

Family	Element (or protein) analyzed	Active or # copies in genome1	From secondary structure, type of DDE/D motif2	Relevant references3
IS1	IS1NISSto9	>40*5	DD(24)EDD(20)E	* Nyman et al., 1981; Ohta et al., 2002, 2004; Siguier et al., 2009
IS1595	1. ISPna2	?,DD(36)N”	Siguier et al., 2009
	2. ISH4	?,DD(36)E”	Siguier et al., 2009
	3. IS1016C	?,DD(34)E”	Siguier et al., 2009
	4. IS1595	?,DD(35)N”	Siguier et al., 2009
	5. ISSod11	13	DD(34)H	Siguier et al., 2009
	6. ISNWi1	?,DD(35)E”	Siguier et al., 2009
	7. ISNha5	?,DD(33)E”	Siguier et al., 2009
	Merlin: MERLIN1_SM	Consensus	DD(36)E	Feschotte, 2004
IS3	IS911	Active	DD(35)E	Polard and Chandler, 1995; Rousseau et al., 2002
IS481	IS481	?00*	DD(35)E	*Glare et al., 1990; Chandler and Mahillon, 2002
IS4	IS50R	Active	PDB ID: 1muhDD(-strand)E	Rezshazy et al., 1993; Davies et al., 2000
IS701	IS701ISRso17	Active (15*)7	DD(-strand)E	*Mazel et al., 1991
ISH3	ISC1359ISC1439A	513	DD(-strand)E
IS1634	IS1634ISMac5ISPlu4	Active (?0*)77	DD(-strand)E	*Vilei et al., 1999
IS5	IS903	Active	DD(65)E	Derbyshire et al., 1987; Rezshazy et al., 1993; Tavakoli et al., 1997
	PIF/Harbinger: PIFa (Z. mays)	Active	DD(59)E	Zhang et al., 2001; Kapitonov and Jurka, 2004; Sinzelle et al., 2008
IS1182	IS660ISPsy6	314	DD(-strand)E	Takami et al., 2001
IS6	IS6100	Active	DD(34)E	Martin et al., 1990; Mahillon and Chandler, 1998
IS21	IS21	Active	DD(45)E	Mahillon and Chandler, 1998; Berger and Haas, 2001
IS30	IS30	Active	DD(33)E	Caspers et al., 1984; Mahillon and Chandler, 1998
IS66	IS679ISPsy5ISMac8	Active333	DD(-helical?)E	Han et al., 2001
IS110	IS492IS1111	Active20	DEDDDEDD	Perkins-Balding et al., 1999; Buchner et al., 2005
IS256	IS256	Active	DD(-helical)E	Mahillon and Chandler, 1998; Prudhomme et al., 2002
	MuDr/Foldback (Mutator)	Active	DD(-helical)E	Eisen et al., 1994; Babu et al., 2006; Hua-Van and Capy, 2008
IS630	ISY100	Active	DD(34)E	Doak et al., 1994; Feng and Colloms, 2007
	Tc1/mariner: Mos1 (D. mauritiana)	Active	PDB ID: 2f7tDD(34)D	Plasterk et al., 1999; Richardson et al., 2006
	Zator: Zator-1_HM	36*	DD(43)E	*Bao et al., 2009
IS982	ISPfu3	5	DD(47)E	Mahillon and Chandler, 1998
IS1380	IS1380A	?00*	DD(-strand)E	*Takemura et al., 1991; Chandler and Mahillon, 2002
	piggyBac (T. ni)	Active	DD(-strand)D	Cary et al., 1989; Sarkar et al., 2003; Mitra et al., 2008
ISAs1	ISAzo3	7	DD(-strand)E/D?
ISL3	IS31831IS651	Active22	DD(-helical)E	Suzuki et al., 2006
Tn3	Tn3 (E. coli)	Active	DD(-helical?)E	Grindley, 2002
hAT	Hermes (M. domestica)	Active	PDB ID: 2bw3 DD(-helical)E insertion	Warren et al., 1994; Rubin et al., 2001; Hickman et al., 2005
CACTA	CACTA1 (A. thaliana) En/Spm ZM	Active	DD(-helical?)E/D?	Miura et al., 2001; DeMarco et al., 2006
P	Drosophila	Active	?	Rio, 2002
Transib	Transib1_AG	Consensus	DD(-helical)E	Kapitonov and Jurka, 2005; Chen and Li, 2008
	RAG1 (M. musculus)	Active	DD(-helical)E	Kim et al., 1999; Landree et al., 1999; Lu et al., 2006
Sola	Sola3-3_HM	Multiple copies*	DD(40)E	*Bao et al., 2009

Hickman AB, Chandler M, Dyda F. Integrating prokaryotes and eukaryotes: DNA transposases in light of structure. Crit Rev Biochem Mol Biol. 2010 Feb;45(1):50-69. doi: 10.3109/10409230903505596.

Classification, distribution and the number of entries of LTR retrotransposons in Repbase

Superfamily	Total
Copia	10,595
Gypsy	6,694
BEL	1,855
ERV
ERV1	1,967
ERV2	1,266
ERV3	657
ERV4	187
Lentivirus	4
Unclassified ERV	325
Unclassified LTR	719
DIRS	418

Classification, and the number of entries of non-LTR retrotransposons in Repbase

Group	Clade	Total
CRE	CRE	43
R2	R4	46
	Hero	23
	NeSL	106
	R2	159
Dualen	RandI/Dualen	13
L1	Proto1	6
	L1	1,690
	Tx1	273
RTE	RTETP	1
	Proto2	47
	RTEX	138
	RTE	487
I	Outcast	23
	Ingi	17
	Vingi	141
	I	195
	Nimb	108
	Tad1	141
	Loa	74
	R1	237
	Jockey	243
CR1	Rex1	95
	CR1	803
	Kiri	91
	L2	285
	L2A	5
	L2B	27
	Crack	140
	Daphne	227
Ambal	Ambal	8
Penelope	Penelope	477
SINE	SINE1/7SL	95
	SINE2/tRNA	539
	SINE3/5S	30
	SINEU	17
	Unclassified SINE	112
	Unclassified non-LTR retrotransposon	179
	Total	7,341

Reference: Kenji K. Kojima, Structural and sequence diversity of eukaryotic transposable elements, Genes & Genetic Systems, 2019, Volume 94, Issue 6, Pages 233-252

Proposal of TE classes with some members having a DNA transposon phenotype

Reference: Benoît Piégu, Solenne Bire, Peter Arensburger, Yves Bigot, A survey of transposable element classification systems – A call for a fundamental update to meet the challenge of their diversity and complexity,
Molecular Phylogenetics and Evolution, Volume 86, 2015, Pages 90-109,
ISSN 1055-7903, https://doi.org/10.1016/j.ympev.2015.03.009.

Major Features of Prokaryotes IS families (ISfinder)

Overview of common transposon annotation tools

	Approach			Class I			Class II
Name		Novo.	Struc.	Simil.	LTR	LINE	SINE	TIR	HEL	MITE
RepeatMasker		x		x	x	x	x	x	x	x
RepeatModeler		x			x	x	x	x	x	x
CLARI_TE	(107)	x	x	x	x	x	x	x	x	x
TESeeker	(41)			x	x	x	x	x	x	x
PILER	(40)	x			x	x	x	x	x	x
Censor	(108)	x			x	x	x	x	x	x
RepLong	(109)	x			x	x	x	x	x	x
EDTA	(44)	x	x	x	x	x	x	x	x	x
MGEScan	(110)	x	x	x	x	x	x
LTR_Finder	(111)		x		x
LtrDetector	(112)		x		x
LTRpred	(73)	x	x	x	x
LTRharvest	(66)	x	x	x	x
LTRdigest	(113)		x		x
SINE-Finder	(68)	x	x				x
SINE-Scan	(69)	x	x				x
TIRvish	(67)		x					x
HelitronScanner	(42)		x						x
MUSTv2	(70)		x							x
MiteFinderII	(71)		x							x
MITE-Tracker	(72)		x							x
detectMITE	(45)		x							x
MITE-Hunter	(47)		x							x
TransposonUltimate

Distribution of TEs across the eukaryote phylogeny

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