PMID- 37264071
OWN - NLM
STAT- MEDLINE
DCOM- 20230605
LR  - 20230607
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 6
IP  - 1
DP  - 2023 Jun 1
TI  - Production of recombinant human IgG1 Fc with beneficial N-glycosylation pattern 
      for anti-inflammatory activity using genome-edited chickens.
PG  - 589
LID - 10.1038/s42003-023-04937-5 [doi]
LID - 589
AB  - Intravenous immunoglobulin (IVIG) is a plasma-derived polyclonal IgG used for 
      treatment of autoimmune diseases. Studies show that alpha-2,6 sialylation of the Fc 
      improves anti-inflammatory activity. Also, afucosylation of the Fc efficiently 
      blocks FcgammaRIIIA by increasing monovalent affinity to this receptor, which can be 
      beneficial for treatment of refractory immune thrombocytopenia (ITP). Here, we 
      generated genome-edited chickens that synthesize human IgG1 Fc in the liver and 
      secrete alpha-2,6 sialylated and low-fucosylated human IgG1 Fc (rhIgG1 Fc) into serum 
      and egg yolk. Also, rhIgG1 Fc has higher affinity for FcgammaRIIIA than commercial 
      IVIG. Thus, rhIgG1 Fc efficiently inhibits immune complex-mediated FcgammaRIIIA 
      crosslinking and subsequent ADCC response. Furthermore, rhIgG1 Fc exerts 
      anti-inflammatory activity in a passive ITP model, demonstrating chicken liver 
      derived rhIgG1 Fc successfully recapitulated efficacy of IVIG. These results show 
      that genome-edited chickens can be used as a production platform for rhIgG1 Fc 
      with beneficial N-glycosylation pattern for anti-inflammatory activities.
CI  - (c) 2023. The Author(s).
FAU - Park, Jin Se
AU  - Park JS
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea.
AD  - Avinnogen Co., Ltd, 1 Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea.
FAU - Choi, Hee Jung
AU  - Choi HJ
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea.
FAU - Jung, Kyung Min
AU  - Jung KM
AUID- ORCID: 0000-0002-5791-2655
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea.
FAU - Lee, Kyung Youn
AU  - Lee KY
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea.
FAU - Shim, Ji Hyeon
AU  - Shim JH
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea.
FAU - Park, Kyung Je
AU  - Park KJ
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea.
FAU - Kim, Young Min
AU  - Kim YM
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea.
AD  - Avinnogen Co., Ltd, 1 Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea.
FAU - Han, Jae Yong
AU  - Han JY
AUID- ORCID: 0000-0003-3413-3277
AD  - Department of Agricultural Biotechnology and Research Institute of Agriculture 
      and Life Sciences, Seoul National University, Seoul, Republic of Korea. 
      jaehan@snu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230601
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Anti-Inflammatory Agents)
SB  - IM
MH  - Humans
MH  - Animals
MH  - *Immunoglobulin G
MH  - *Immunoglobulins, Intravenous/pharmacology
MH  - Chickens/metabolism
MH  - Glycosylation
MH  - Anti-Inflammatory Agents/pharmacology
PMC - PMC10235082
COIS- The authors declare no competing interests.
EDAT- 2023/06/02 01:07
MHDA- 2023/06/05 06:42
PMCR- 2023/06/01
CRDT- 2023/06/01 23:21
PHST- 2022/04/28 00:00 [received]
PHST- 2023/05/12 00:00 [accepted]
PHST- 2023/06/05 06:42 [medline]
PHST- 2023/06/02 01:07 [pubmed]
PHST- 2023/06/01 23:21 [entrez]
PHST- 2023/06/01 00:00 [pmc-release]
AID - 10.1038/s42003-023-04937-5 [pii]
AID - 4937 [pii]
AID - 10.1038/s42003-023-04937-5 [doi]
PST - epublish
SO  - Commun Biol. 2023 Jun 1;6(1):589. doi: 10.1038/s42003-023-04937-5.