• Asian-Australasian Journal of Animal Sciences
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• 제14권10호
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• pp.1497-1504
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• 2001

There is emerging interest in using xenotransplantation of porcine cells, tissues and organs for treatment of human illness. This article reviews the current status of xenotransplantation, with particular emphasis on the physiological and immunological barriers to xenotransplantation and genetic manipulations to overcome xenograft rejection. Preliminary success in xenotransplantation therapy for human Parkinson's disease using porcine foetal brain cells is described. Finally the zoonotic dangers of porcine xenotransplantation, most particularly porcine endogenous retroviruses (PERVs), are discussed.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2001년도 공동 춘계학술대회
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• pp.52.1-52
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• 2001

No Abstract, See Full Text

• Asian-Australasian Journal of Animal Sciences
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• 제25권10호
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• pp.1357-1363
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• 2012

Pigs may need to be exploited as xenotransplantation donors due to the shortage of human organs, tissues and cells. Porcine endogenous retroviruses (PERVs) are a significant obstacle to xenotransplantation because they can infect human cells in vitro and have the potential for transmission of unexpected pathogens to humans. In this research, 101 pigs, including four commercial breeds (23 Berkshire, 13 Duroc, 22 Landrace and 14 Yorkshire pigs), one native breed (19 Korean native pigs) and one miniature breed (10 NIH miniature pigs) were used to investigate insertional variations for 11 PERV loci (three PERV-A, six PERV-B and two PERV-C). Over 60% of the pigs harbored one PERV-A (907F8) integration and five PERV-B (B3-3G, B3-7G, 742H1, 1155D9 and 465D1) integrations. However, two PERV-A loci (A1-6C and 1347C1) and one PERV-B locus (B3-7F) were absent in Duroc pigs. Moreover, two PERV-C loci (C2-6C and C4-2G) only existed in Korean native pigs and NIH miniature pigs. The results suggest that PERV insertional variations differ among pig breeds as well as among individuals within a breed. Also, the results presented here can be used for the selection of animals that do not have specific PERV integration for xenotransplantation research.

• Asian-Australasian Journal of Animal Sciences
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• 제20권4호
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• pp.461-465
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• 2007

Porcine Endogenous Retroviruses (PERVs) are a major concern in relation to xenotransplantation. Previous research indicated that PERVs are present at about 50 copies in the pig genome and their chromosomal insertion sites are different among pig breeds. We examined nine Korean native pigs and seven Asian Wild Boars for the presence of a PERV-A at SSC 1q2.4 and a PERV-B at SSC 7p1.1-2 previously reported in a Large White pig. The PERV-B at locus 7p1.1-2 displayed insertional variability in Korean native pigs and Asian Wild Boars. Using the primers for the PERV-A at 1q2.4 from Large White pig, we only can amplify an unclassified 798 bp sequence, which showed insertional variability only in Korean native pigs. This study indicates that there are differences within and between Asian and European pigs in PERV insertions and suggests that selection could generate PERV-free lines of pigs more suitable for xenotransplantation.

• 한국융합학회논문지
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• 제8권6호
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• pp.275-281
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• 2017

인간 내인성 레트로 바이러스는 약 3~4 천만 년 전 인간게놈에 통합되기 시작했던 화석바이러스로서 인간게놈의 약 8%를 구성하고 있다. 이러한 고대의 레트로 바이러스는 연속된 유전자변이로 인해 본래의 기능을 잃게 됨으로써 "쓸모없는 DNA (junk DNA)"로 여겨져 왔다. 그러나 최근 연구는 모든 인간 내인성 레트로 바이러스가 단지 침묵을 지키는 승객만이 아님을 보여준다. 현재까지는 이들 바이러스가 인간 질병의 직접 원인이 된다는 것은 밝혀지지 않았으나, 다발성 경화증, 정신 분열증 및 근 위축성 측삭경화증을 포함한 신경학적 장애와 인간면 역결핍바이러스 (HIV)나 헤르페스 등의 바이러스 감염, 여러 유형의 암과 같은 질환을 가진 환자에서 인간 내인성 레트로 바이러스의 DNA가 과도발현 됨을 보여주는 연구들이 다양하게 이루어지고 있다. 이 리뷰논문은 신경학적 질환에 대한 인간 내인성 레트로 바이러스의 가능한 관련여부를 다루고 있다.

• 농업과학연구
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• 제38권1호
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• pp.71-77
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• 2011

Pigs have anatomically and physiologically very similar to human and because of this, pigs are the possible xenotransplantation donors for human organs. PERVs (Porcine Endogenous Retroviruses) are known to be one of the possible obstacles for using porcine organs regardless of the immunological barriers. In order to understand the expression patterns of PERVs in Korean native pigs, we investigated PERV expressions in porcine liver, heart, spleen, and lung samples. After RNA extraction, two types of specific PERV envelope genes (ENV-A and ENV-B) were amplified using specific primers by RT-PCR. The results indicated that the variable PERV expressions were observed in inconsistent patterns among animals and tissues. The PERV expressions were verified with semi-quantitative real-time PCR with three replicates. Even though, these results confirm the previous findings that the PERVs were differentially expressed between animals and tissues. These results also give some valuable information for xenotransplantation when using the Korean native pigs as the organ donor.

• Molecules and Cells
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• 제24권1호
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• pp.148-151
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• 2007

Porcine endogenous retroviruses (PERVs) in the pig genome represent a potential risk of infection in pig-to-human transplantation and are transmitted vertically. The solitary long terminal repeat (LTR) elements of the PERVs affect the replication properties of the individual viruses via their repeat sequences and by encoding a set of specific transcription factors. We examined the promoter activities of solitary LTR elements belonging to the PERV-A and -B families of the Korean domestic pig (KDP) using luciferase reporters. Three of the LTR structures (of PERV-A5-KDP, PERV-A7-KDP, PERV-A8-KDP) had different promoter activities in human HCT116 cells and monkey Cos7 cells, and potential negatively and positively acting regions affecting transcription were identified by deletion analysis. These data suggest that specific sequences in the U3 region of a given LTR element can affect the activities of promoter or enhancer elements in the PERV.

• Molecules and Cells
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• 제40권10호
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• pp.796-804
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• 2017

Endogenous retroviruses (ERVs) have been integrated into vertebrate genomes and have momentously affected host organisms. Horses (Equus caballus) have been domesticated and selected for elite racing ability over centuries. ERVs played an important role in the evolutionary diversification of the horse genome. In the present study, we identified six equine ERV families (EqERVs-E1, I1, M2, P1, S1, and Y4), their full-length viral open reading frames (ORFs), and elucidated their phylogenetic relationships. The divergence time of EqERV families assuming an evolutionary rate of 0.2%/Myr indicated that EqERV-S3 (75.4 million years ago; mya) on chromosome 10 is an old EqERV family and EqERV-P5 (1.2 Mya) on chromosome 12 is a young member. During the evolutionary diversification of horses, the EqERV-I family diverged 1.7 Mya to 38.7 Mya. Reverse transcription quantitative real-time PCR (RT-qPCR) amplification of EqERV pol genes showed greater expression in the cerebellum of the Jeju horse than the Thoroughbred horse. These results could contribute further dynamic studies for horse genome in relation to EqERV gene function.

• IMMUNE NETWORK
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• 제1권1호
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• pp.45-52
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• 2001

Background: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. Methods: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. Results: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X $10^6CFU/ml4$. After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. Conclusions: The results suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2003년도 제39회 학술심포지움
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• pp.99-99
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• 2003