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Review Article

Embryo-Engineered Nonhuman Primate Models: Progress and Gap to Translational Medicine

Table 1

NHPs models constructed by different methods.

Type of modelsYearSpeciesMethodGeneStagesSamplesImplanted blastocystsPregnancy rateTotal neonatusModelsMutation rateContributionAuthor/reference

Viral vector-mediated transgenic2001Rhesus monkeysRetroviral vectorGFPMature oocytes224 oocytes403133%The first transgenic monkeyChan et al. [17]
2008Rhesus monkeysLentivirus vectorHTT-84Q and GFPMature oocytes130 oocytes3055100%The first monkey model of HDYang et al. [23]
2009Common marmosetsLentiviral vectorEGFPPreimplantation embryos201 embryos9155100%The first germline transmissionSasaki et al. [18]
2010Rhesus monkeysLentiviral vectorEGFPEarly cleavage-stage embryos70 embryos305240%The first transgenic monkey in ChinaNiu et al. [26]
2015Rhesus monkeysLentiviral vectorα-Syn (A53T)Mature oocytes133 oocytes757686%The first monkey model of PDNiu et al. [27]
2016Cynomolgus monkeysLentiviral vectorMECP2Mature oocytesFirst: 94 oocytes; second: 264 oocytes53
105
; 8; 2Total 880%The monkey model of autism-like diseaseLiu et al. [28]
2016Cynomolgus monkeysLentiviral vectorGFP24 hours after ICSI; 4 hours before ICSI18; 695; 17; 0; 20; 20%; 100%Construction of cynomolgus monkeys expressing GFPSeita et al. [25]
2019Rhesus monkeysLentivirus vectorMCPH1Early cleavage-stage embryos66100%The huMCPH1 transgenic monkeyShi et al. [30]

TALEN or ZFN knockout2014Rhesus monkeys and cynomolgus monkeysTALENMECP2One-cell embryosRhesus: 59 embryos cynomolgus: 86 embryos21; 54; 0; 1Total 4The first monkey model of RTT; the first monkey model of TALENLiu et al. [33]
2017Cynomolgus monkeysTALENMECP2One-cell embryos123 embryos1237686%Research on RTTChen et al. [34]
2016Cynomolgus monkeysTALENMCPH1Embryos55 embryos523133%The first monkey model of human microcephalyKe et al. [19]
2016Common marmosetsZFN and TALENIL2RGPronuclear stage embryos250 embryos17921943%The first monkey model of ZFN; the first monkey model of X-SCIDSato et al. [35]

CRISPR/Cas9 knockout2014Cynomolgus monkeysCRISPR/Cas9Pparg and Rag1One-cell embryos186 zygotes835240%The first monkey model of CRISPR/Cas9Niu et al. [36, 37]
2015Cynomolgus monkeysCRISPR/Cas9P53Zygotes108 zygotes623267%The first live p53 biallelic mutant monkeyWan et al. [20]
2015Rhesus monkeysCRISPR/Cas9DystrophinZygotes488 embryos17914964%The first monkey model of DMDChen et al. [38]
2015Cynomolgus monkeysCRISPR/Cas9Nr0b1 (Dax1)One-cell embryos186 zygotes835The first monkey model of AHC-HHKang et al. [39]
2017Cynomolgus monkeysCRISPR/Cas9SHANK3One-cell embryos116 embryos11611100%The first monkey model of ASDZhao et al. [45]
2018Cynomolgus monkeysCRISPR/Cas9SIRT6Zygotes98 zygotes4833100%The first monkey model of perinatal lethality syndromeZhang et al. [46]
2019Cynomolgus monkeysCRISPR/Cas9SHANK3Embryos178 embryos1789556%Monkey model of ASD and Phelan–McDermid syndromeZhou et al. [47]
2019Cynomolgus monkeysCRISPR/Cas9BMAL1Zygotes88 embryos888563%The first monkey model of circadian and psychiatric disordersQiu et al. [48]
2019Cynomolgus monkeysCRISPR/Cas9PKD1Embryos423 embryos861419The first monkey model of ADPKDTsukiyama et al. [49]
2019Rhesus monkeysCRISPR/Cas9PINK1One-cell embryos158 embryos8711873%Monkey model of PDYang et al. [50]
2019Cynomolgus monkeysCRISPR/Cas9HBBZygotes97 zygotes2211100%The first monkey model of human β-thalassemiaHuang et al. [51]
2019Rhesus monkeysCRISPR/Cas9SHANK3Pronuclear-stage embryosmRNA: 22; nuclease: 26Editing efficiency: mRNA:80%; nuclease:100%KI/KO efficiency verified at embryo levelKumita et al. [54]
c-kitPronuclear stage embryosmRNA: 20; nuclease: 25Editing efficiency: mRNA:77.8%; nuclease:100%

CRISPR/Cas9 knockin2017Cynomolgus monkeysCRISPR/Cas9mCherryZygotesFirst: 26; second: 10First (high-concentration HMEJ donor): 4/5 mCherry+ blastocysts; second (low-concentration HMEJ donor): 1/4 mCherry+ blastocystsVerified HMEJ-based knockin at the embryo levelYao et al. [55]
2018Cynomolgus monkeysCRISPR/Cas9Oct4-GFPZygotes198 zygotes1208113%The first monkey model of KICui et al. [56]
2019Rhesus monkeysCRISPR/Cas9c-kitPronuclear stage embryos40 embryosOptimal injection combination: 36 nt sense ssODN and CRISPR/nuclease mixture; editing efficiency: 30.8%KI/KO efficiency verified at embryo levelKumita et al. [54]

Chimera embryo2015Cynomolgus monkeysRetroviral vectorGFPESC1402The first monkey chimerasChen et al. [22]

SCNT2018Cynomolgus monkeys22100%The first monkey model of SCNTLiu et al. [16]
2019Cynomolgus monkeys32555100%The first disease monkey model of SCNTLiu et al. [64]

BE point mutation2020Cynomolgus monkeysCBELMNAZygotes86 zygotes415480%The first monkey model of BEWang et al. [60]
2020Rhesus monkeysCBEMECP2ZygotesEmbryo levelEstablished a stable embryo editing system of RTTZhou et al. [62]
2020Cynomolgus monkeysCBE and ABEMultiple lociZygotesEmbryo levelSimultaneously edit multiple loci at the embryo levelZhang et al. [63]

Pregnancy rate: ; mutation rate: .