In vivo prime editing of a metabolic liver disease in mice (Record no. 953)
[ view plain ]
042 ## - AUTHENTICATION CODE | |
---|---|
Authentication code | dc |
100 10 - MAIN ENTRY--PERSONAL NAME | |
Personal name | Böck, Desirée |
Relator term | author |
9 (RLIN) | 2742 |
245 00 - TITLE STATEMENT | |
Title | In vivo prime editing of a metabolic liver disease in mice |
260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
Date of publication, distribution, etc. | 2022-03-16. |
500 ## - GENERAL NOTE | |
General note | /pmc/articles/PMC7614134/ |
500 ## - GENERAL NOTE | |
General note | /pubmed/35294257 |
520 ## - SUMMARY, ETC. | |
Summary, etc. | Prime editing is a highly versatile CRISPR-based genome editing technology that works without DNA double-strand break formation. Despite rapid technological advances, in vivo application for the treatment of genetic diseases remains challenging. Here, we developed a size-reduced SpCas9 prime editor (PE) lacking the RNaseH domain (PE2(ΔRnH)) and an intein-split construct (PE2 p.1153) for adeno-associated virus (AAV)-mediated delivery into the liver. Editing efficiencies reached 15% at the Dnmt1 locus, and were further elevated to 58% by delivering unsplit PE2(ΔRnH) via human adenoviral vector 5 (AdV). To provide proof-of-concept for correcting a genetic liver disease, we next employed the AdV approach for repairing the disease-causing Pah(enu2) mutation in a mouse model of phenylketonuria (PKU) via prime editing. Average correction efficiencies of 11.1% (up to 17.4%) in neonates led to therapeutic reduction of blood phenylalanine (L-Phe), without inducing detectable off-target mutations or prolonged liver inflammation. Although the current in vivo prime editing approach for PKU has limitations for clinical application due to the requirement of high vector doses (7×10(14) vg/kg) and the induction of immune responses to the vector and the PE, further development of the technology may lead to curative therapies for PKU and other genetic liver diseases. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | |
546 ## - LANGUAGE NOTE | |
Language note | en |
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
Topical term or geographic name as entry element | Article |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Rothgangl, Tanja |
Relator term | author |
9 (RLIN) | 2743 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Villiger, Lukas |
Relator term | author |
9 (RLIN) | 2744 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Schmidheini, Lukas |
Relator term | author |
9 (RLIN) | 2745 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Matsushita, Mai |
Relator term | author |
9 (RLIN) | 2746 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Mathis, Nicolas |
Relator term | author |
9 (RLIN) | 2747 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Ioannidi, Eleonora |
Relator term | author |
9 (RLIN) | 2748 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Rimann, Nicole |
Relator term | author |
9 (RLIN) | 2749 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Grisch-Chan, Hiu Man |
Relator term | author |
9 (RLIN) | 2750 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Kreutzer, Susanne |
Relator term | author |
9 (RLIN) | 2751 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Kontarakis, Zacharias |
Relator term | author |
9 (RLIN) | 2752 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Kopf, Manfred |
Relator term | author |
9 (RLIN) | 2753 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Thöny, Beat |
Relator term | author |
9 (RLIN) | 2754 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Schwank, Gerald |
Relator term | author |
9 (RLIN) | 2755 |
786 0# - DATA SOURCE ENTRY | |
Note | Sci Transl Med |
856 41 - ELECTRONIC LOCATION AND ACCESS | |
Uniform Resource Identifier | <a href="http://dx.doi.org/10.1126/scitranslmed.abl9238">http://dx.doi.org/10.1126/scitranslmed.abl9238</a> |
Public note | Connect to this object online. |
No items available.