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Base Editing-Enabled Technologies and Multiplex Genome Editing
Base Editing-Enabled Technologies and Multiplex Genome Editing
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103604
- ISBN
- 9798280721036
- DDC
- 610
- 저자명
- Volf, Verena.
- 서명/저자
- Base Editing-Enabled Technologies and Multiplex Genome Editing
- 발행사항
- [Sl] : Harvard University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 241 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Church, George.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2025.
- 초록/해제
- 요약Base editing is a precision genome editing technology that enables targeted single-nucleotide changes without requiring double-strand DNA breaks. This dissertation presents several distinct advances in multiplex base editing and base editing-enabled technologies in mammalian systems. First, we demonstrate large-scale editing of transposable elements, which can be targeted with a single guide RNA due to their repetitive nature. Using catalytically inactive Cas9 base editors, which minimize editing-associated cytotoxicity, we achieve several thousand edits per cell. Second, we develop Genomic Sequence Encryption (GSE), a cryptographic framework that uses multiplex base editing and pooled guide RNAs to encode information across more than one hundred distinct genomic loci. We implement GSE in mammalian cell lines and stem cells, establishing a robust method for introducing a high number of edits in both bulk populations and individual stem cells. We devise an enrichment strategy that enables the isolation of stem cells carrying more than two dozen distinct precision edits across a single diploid genome with minimal screening. This represents a significant advancement in the scale of simultaneous precision editing achievable in primary or stem cells, and, in the context of GSE, paves the way for encrypted genomic signatures in living animals. Lastly, we develop reprogrammable ADAR sensors, a programmable RNA-sensing platform that links endogenous transcript detection to protein translation through A-to-I RNA editing. Together, these contributions expand the scope of base editing by enabling large-scale genome modification, secure biological information encoding, and transcript-responsive regulation in mammalian cells.
- 일반주제명
- Bioengineering
- 일반주제명
- Genetics
- 일반주제명
- Biomedical engineering
- 키워드
- Base editing
- 기타저자
- Harvard University Engineering and Applied Sciences - Engineering Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520260202103604
■006m o d
■007cr#unu||||||||
■020 ▼a9798280721036
■035 ▼a(MiAaPQ)AAI32042684
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a610
■1001 ▼aVolf, Verena.▼0(orcid)0000-0001-7305-3873
■24510▼aBase Editing-Enabled Technologies and Multiplex Genome Editing
■260 ▼a[Sl]▼bHarvard University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a241 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Church, George.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2025.
■520 ▼aBase editing is a precision genome editing technology that enables targeted single-nucleotide changes without requiring double-strand DNA breaks. This dissertation presents several distinct advances in multiplex base editing and base editing-enabled technologies in mammalian systems. First, we demonstrate large-scale editing of transposable elements, which can be targeted with a single guide RNA due to their repetitive nature. Using catalytically inactive Cas9 base editors, which minimize editing-associated cytotoxicity, we achieve several thousand edits per cell. Second, we develop Genomic Sequence Encryption (GSE), a cryptographic framework that uses multiplex base editing and pooled guide RNAs to encode information across more than one hundred distinct genomic loci. We implement GSE in mammalian cell lines and stem cells, establishing a robust method for introducing a high number of edits in both bulk populations and individual stem cells. We devise an enrichment strategy that enables the isolation of stem cells carrying more than two dozen distinct precision edits across a single diploid genome with minimal screening. This represents a significant advancement in the scale of simultaneous precision editing achievable in primary or stem cells, and, in the context of GSE, paves the way for encrypted genomic signatures in living animals. Lastly, we develop reprogrammable ADAR sensors, a programmable RNA-sensing platform that links endogenous transcript detection to protein translation through A-to-I RNA editing. Together, these contributions expand the scope of base editing by enabling large-scale genome modification, secure biological information encoding, and transcript-responsive regulation in mammalian cells.
■590 ▼aSchool code: 0084.
■650 4▼aBioengineering
■650 4▼aGenetics
■650 4▼aBiomedical engineering
■653 ▼aBase editing
■653 ▼aGenomic cryptography
■653 ▼aMulti-site editing
■653 ▼aMultiplex editing
■653 ▼aPrecision editing
■690 ▼a0202
■690 ▼a0369
■690 ▼a0541
■71020▼aHarvard University▼bEngineering and Applied Sciences - Engineering Sciences.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357820▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
