Robust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1

Abstract With recent advancements in gene editing technology using the CRISPR/Cas system, there is a demand for more effective gene editors. A key factor facilitating efficient gene editing is effective CRISPR delivery into cells, which is known to be associated with the size of the CRISPR system. A...

Full description

Saved in:
Bibliographic Details
Main Authors: Soo-Ji Park, Sungjin Ju, Won Jun Jung, Tae Yeong Jeong, Da Eun Yoon, Jang Hyeon Lee, Jiyun Yang, Hojin Lee, Jungmin Choi, Hyeon Soo Kim, Kyoungmi Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56048-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832594587784314880
author Soo-Ji Park
Sungjin Ju
Won Jun Jung
Tae Yeong Jeong
Da Eun Yoon
Jang Hyeon Lee
Jiyun Yang
Hojin Lee
Jungmin Choi
Hyeon Soo Kim
Kyoungmi Kim
author_facet Soo-Ji Park
Sungjin Ju
Won Jun Jung
Tae Yeong Jeong
Da Eun Yoon
Jang Hyeon Lee
Jiyun Yang
Hojin Lee
Jungmin Choi
Hyeon Soo Kim
Kyoungmi Kim
author_sort Soo-Ji Park
collection DOAJ
description Abstract With recent advancements in gene editing technology using the CRISPR/Cas system, there is a demand for more effective gene editors. A key factor facilitating efficient gene editing is effective CRISPR delivery into cells, which is known to be associated with the size of the CRISPR system. Accordingly, compact CRISPR-Cas systems derived from various strains are discovered, among which Un1Cas12f1 is 2.6 times smaller than SpCas9, providing advantages for gene therapy research. Despite extensive engineering efforts to improve Un1Cas12f1, the editing efficiency of Un1Cas12f1 is still shown to be low depending on the target site. To overcome this limitation, we develop enhanced Cas12f1 (eCas12f1), which exhibits gene editing activity similar to SpCas9 and AsCpf1, even in gene targets where previously improved Un1Cas12f1 variants showed low gene editing efficiency. Furthermore, we demonstrate that eCas12f1 efficiently induces apoptosis in cancer cells and is compatible with base editing and regulation of gene expression, verifying its high utility and applicability in gene therapy research.
format Article
id doaj-art-e8dc0c404a8b4842975241f58eaca0df
institution Kabale University
issn 2041-1723
language English
publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-e8dc0c404a8b4842975241f58eaca0df2025-01-19T12:31:30ZengNature PortfolioNature Communications2041-17232025-01-0116111210.1038/s41467-025-56048-wRobust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1Soo-Ji Park0Sungjin Ju1Won Jun Jung2Tae Yeong Jeong3Da Eun Yoon4Jang Hyeon Lee5Jiyun Yang6Hojin Lee7Jungmin Choi8Hyeon Soo Kim9Kyoungmi Kim10Department of Physiology, Korea University College of MedicineDepartment of Physiology, Korea University College of MedicineDepartment of Physiology, Korea University College of MedicineDepartment of Physiology, Korea University College of MedicineDepartment of Physiology, Korea University College of MedicineDepartment of Physiology, Korea University College of MedicineDepartment of Physiology, Korea University College of MedicineDepartment of Biomedical Sciences, Korea University College of MedicineDepartment of Biomedical Sciences, Korea University College of MedicineDepartment of Biomedical Sciences, Korea University College of MedicineDepartment of Physiology, Korea University College of MedicineAbstract With recent advancements in gene editing technology using the CRISPR/Cas system, there is a demand for more effective gene editors. A key factor facilitating efficient gene editing is effective CRISPR delivery into cells, which is known to be associated with the size of the CRISPR system. Accordingly, compact CRISPR-Cas systems derived from various strains are discovered, among which Un1Cas12f1 is 2.6 times smaller than SpCas9, providing advantages for gene therapy research. Despite extensive engineering efforts to improve Un1Cas12f1, the editing efficiency of Un1Cas12f1 is still shown to be low depending on the target site. To overcome this limitation, we develop enhanced Cas12f1 (eCas12f1), which exhibits gene editing activity similar to SpCas9 and AsCpf1, even in gene targets where previously improved Un1Cas12f1 variants showed low gene editing efficiency. Furthermore, we demonstrate that eCas12f1 efficiently induces apoptosis in cancer cells and is compatible with base editing and regulation of gene expression, verifying its high utility and applicability in gene therapy research.https://doi.org/10.1038/s41467-025-56048-w
spellingShingle Soo-Ji Park
Sungjin Ju
Won Jun Jung
Tae Yeong Jeong
Da Eun Yoon
Jang Hyeon Lee
Jiyun Yang
Hojin Lee
Jungmin Choi
Hyeon Soo Kim
Kyoungmi Kim
Robust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1
Nature Communications
title Robust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1
title_full Robust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1
title_fullStr Robust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1
title_full_unstemmed Robust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1
title_short Robust genome editing activity and the applications of enhanced miniature CRISPR-Cas12f1
title_sort robust genome editing activity and the applications of enhanced miniature crispr cas12f1
url https://doi.org/10.1038/s41467-025-56048-w
work_keys_str_mv AT soojipark robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT sungjinju robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT wonjunjung robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT taeyeongjeong robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT daeunyoon robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT janghyeonlee robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT jiyunyang robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT hojinlee robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT jungminchoi robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT hyeonsookim robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1
AT kyoungmikim robustgenomeeditingactivityandtheapplicationsofenhancedminiaturecrisprcas12f1