JOM KITA KE POLITEKNIK

In vivo prime editing of a metabolic liver disease in mice (Record no. 2242)

MARC details
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.