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基因编辑与再生医学的界面

The Interface of Gene Editing with Regenerative Medicine.

作者信息

Farag Veronica E, Devey Elsie A, Leong Kam W

机构信息

Department of Biomedical Engineering, Columbia University, New York City, NY 10027, USA.

Department of Systems Biology, Columbia University, New York City, NY 10032, USA.

出版信息

Engineering (Beijing). 2025 Mar;46:73-100. doi: 10.1016/j.eng.2024.10.019. Epub 2024 Nov 30.


DOI:10.1016/j.eng.2024.10.019
PMID:40881775
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12382428/
Abstract

The potential of regenerative medicine in the clinical space is vast, given its ability to repair and replace damaged tissues, restore lost functions due to age or disease, and transform personalized therapy. Traditional regenerative medicine and tissue engineering strategies have created specialized tissues using progenitor cells and various biological stimuli. To date, there are many US Food and Drug Administration (FDA)-approved regenerative medicine therapies, such as those for wound healing and orthopedic injuries. Nonetheless, these therapies face challenges, including off-target effects, a lack of precision, and failure to target the disease or injury at its origin. In search of novel, precise, and efficient alternatives, the regenerative medicine landscape is shifting towards genome engineering technologies, particularly gene editing. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing systems enable precise knock-ins, knockouts, transcriptional activation and repression, as well as specific base conversions. This advancement has allowed researchers to treat genetic and degenerative diseases, control cell fate for highly regulated tissue repair, and enhance tissue functions. In this review, we explore the progress and future prospects of CRISPR technologies in regenerative medicine, focusing on how gene editing has led to advanced therapeutic applications and served as a versatile research tool for understanding tissue development and disease progression.

摘要

鉴于再生医学具有修复和替换受损组织、恢复因年龄或疾病而丧失的功能以及变革个性化治疗的能力,其在临床领域的潜力巨大。传统的再生医学和组织工程策略利用祖细胞和各种生物刺激创造了专门的组织。迄今为止,有许多美国食品药品监督管理局(FDA)批准的再生医学疗法,例如用于伤口愈合和骨科损伤的疗法。尽管如此,这些疗法面临着挑战,包括脱靶效应、缺乏精准性以及未能从根源上针对疾病或损伤。为了寻找新颖、精准且高效的替代方法,再生医学领域正在转向基因组工程技术,尤其是基因编辑。基于成簇规律间隔短回文重复序列(CRISPR)的基因编辑系统能够实现精确的基因插入、敲除、转录激活和抑制,以及特定的碱基转换。这一进展使研究人员能够治疗遗传和退行性疾病、控制细胞命运以实现高度可控的组织修复,并增强组织功能。在本综述中,我们探讨CRISPR技术在再生医学中的进展和未来前景,重点关注基因编辑如何带来先进的治疗应用,并作为理解组织发育和疾病进展的通用研究工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/485fa5aff5f9/nihms-2086763-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/9e8fc8efca44/nihms-2086763-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/9a82668e3b69/nihms-2086763-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/0f6c6f770874/nihms-2086763-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/12f779d1d9f7/nihms-2086763-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/60d51970db23/nihms-2086763-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/485fa5aff5f9/nihms-2086763-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/9e8fc8efca44/nihms-2086763-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/9a82668e3b69/nihms-2086763-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/0f6c6f770874/nihms-2086763-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/12f779d1d9f7/nihms-2086763-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/60d51970db23/nihms-2086763-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8fd/12382428/485fa5aff5f9/nihms-2086763-f0006.jpg

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[1]
The Interface of Gene Editing with Regenerative Medicine.

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[2]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Improvements in Health-Related Quality of Life in Patients with Transfusion-Dependent β-Thalassemia After Exagamglogene Autotemcel.

Blood Adv. 2025-8-19

[2]
Brain Chimeroids reveal individual susceptibility to neurotoxic triggers.

Nature. 2024-7

[3]
DNA shape features improve prediction of CRISPR/Cas9 activity.

Methods. 2024-6

[4]
On- and off-target effects of paired CRISPR-Cas nickase in primary human cells.

Mol Ther. 2024-5-1

[5]
Selection of extended CRISPR RNAs with enhanced targeting and specificity.

Commun Biol. 2024-1-12

[6]
Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1.

EMBO Mol Med. 2024-1

[7]
piCRISPR: Physically informed deep learning models for CRISPR/Cas9 off-target cleavage prediction.

Artif Intell Life Sci. 2023-12

[8]
TREX2 enables efficient genome disruption mediated by paired CRISPR-Cas9 nickases that generate 3'-overhanging ends.

Mol Ther Nucleic Acids. 2023-11-2

[9]
CRISPR/Cas9 Directed Reprogramming of iPSC for Accelerated Motor Neuron Differentiation Leads to Dysregulation of Neuronal Fate Patterning and Function.

Int J Mol Sci. 2023-11-10

[10]
Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models.

Nat Commun. 2023-11-11

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