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Unpublished conference/Abstract (Scientific congresses and symposiums)
Towards a new, glyco-humanized rabbit line.
Van Laere, Anne-Sophie; Martin, Ludivine; M'Boumba, Jessy et al.
2023FARAH Day
 

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Keywords :
genetic engineering; CRISPR/Cas9; rabbit
Abstract :
[en] Humans lack Neu5Gc and αGal moieties on glycosylated proteins due to mutations in the enzymes CMAH and GGTA1, respectively. For a variety of reasons, rabbits produce exquisitely effective antibodies that are suitable for use as human therapeutics. However, as they display these Neu5Gc and aGal epitopes, a strong humoral response is elicited upon injection in humans, which reduces clinical efficacy and shortens half-life. In this context and in accordance with the scope of our University, FEDER-backed EPI-SHIELD initiative, we aimed at inactivating CMAH and GGTA1, relying on the CRISPR/Cas9 technology. Six-month old, superovulated does were sacrificed and their zygotes harvested ~14 hours after mating. A mix of 2 ribonucleoproteins, each made of Cas9 and a specific guide-RNA, was injected in the pronucleus, and injected embryos were either cultured for 5 days (up to the blastocyst stage) or transferred in the oviducts of a synchronized, pseudopregnant doe. High proportions of five-day old blastocysts displayed indels at expected locations, with success rates of ~43 (3/7) and ~71% (5/7) for GGTA1 and CMAH, respectively. After transfer, a litter of 4 kits was born. Among the 4 kits, the CMAH of one is expected to be inactivated, due to insertion of a single G generating a premature stop codon.
Research Center/Unit :
FARAH - Fundamental and Applied Research for Animals and Health - ULiège
Disciplines :
Genetics & genetic processes
Author, co-author :
Martin, Ludivine ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
M'Boumba, Jessy ;  Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Ectors, Fabien  ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Desmecht, Daniel ;  Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Speaker :
Van Laere, Anne-Sophie  ;  Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Language :
English
Title :
Towards a new, glyco-humanized rabbit line.
Publication date :
21 December 2023
Event name :
FARAH Day
Event date :
21/12/2023
References of the abstract :
Proceedings of the 10th FARAH-Day
Name of the research project :
EPI-SHIELD : Création accélérée de biosolutions anti-infectieuses super-diversifiées et leur fabrication low-cost
Funders :
FEDER - Fonds Européen de Développement Régional
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since 09 January 2024

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