인간 유전체 연구 관련 국제 특허성 연구(I) : 유전자 단편, 유전자 진단, 체세포 유전자 치료를 중심으로

김소윤 ( Kim So-yoon ),김수민 ( Kim Su-min ),김한나 ( Kim Han-nah ) 한국의료법학회 2016 한국의료법학회지 Vol.24 No.2

이 논문의 목적은 인간 유전체 연구의 특허와 관련된 국제 동향을 유전자 단편, 유전자 진단, 체세포 유전자 치료를 중심으로 살펴보고 그 연구 결과를 고찰해 보는 것이다. 최근 생명공학 특허 분야에서 논란이 되었던 것은 유전자 단편에 대한 특허성 인정에 대한 것이다. 이전까지 당연히 인정되었던 유전자 단편의 특허가 기술의 발전에 따라 미국을 선두로 그 특허성이 인정되지 않는 추세로 바뀜에 따라 국제적으로 영향이 나타나고 있다. 이를 살펴보기 위하여, 먼저 이 논문은 우선유전자 단편, 유전자 진단 및 체세포 유전자 치료의 최신 연구 동향을 소개하였다. 또한 저자들은 분야별 각 국가의 특허 제도의 동향에 대해 조사하고 그 분석 결과를 고찰하였다. 연구 결과, 국가별로 인간 유전체 연구의 특허 허여 여부의 기준에 있어 조금씩 차이를 보이고 있었다. 첫째, 유전자 단편의 특허성은 관련 기술의 발전과 미국 연방대법원 등으로 인하여 점차 그 의미가 퇴색될 것으로 보이므로 우리 제도에서도 제고가 필요하다. 둘째, 유전자 진단의 경우, 미국은 의료행위 또한 특허 대상으로 보기 때문에 유전자 진단 방법도 특허 가능할 것으로 보이나, 대부분의 국가에서 체외 진단기기나 비의료행위의 관점에서 특허성을 인정하고 있으며, 우리 특허 제도에서도 큰 문제가 없다고 본다. 셋째, 체세포 유전자 치료는 모든 연구 대상 국가에서 치료제로 구분하여 기존의 의약품과 마찬가지로 특허대상으로 보고 있다. This article aims to examine international trend related patentability of human genome researches focusing on gene segment, genetic diagnosis, and somatic gene therapy, and then review the research results. Recently in biotechnology area the patentability of gene segment arouse controversy. Previously patentability of gene segment was rightly acknowledged but with the development of biotechnology, leading by U.S., the gene segment turned out unpatentable, and it affects internationally. To examine this tendency more in-depth, first of all this article introduce the recent research trend of gene segment, genetic diagnosis, and somatic gene therapy. Then researchers investigate each country’s trend of patent system in human genome researches and review the result of analysis. Consequently, each country has slightly different standards in patentability on human gaenome researches. First, the patentability of gene segment’s meaning will be faded by affected the development of biotechnology and sharing international gene database, so our system’s improvement is needed. Second, in case of genetic diagnosis, in U.S., the medical practice is patentable so as to genetic diagnosis, but most countries accept the patentability of genetic diagnosis in the point of in vitro medical devices or non-medical practices, and it is same as in our patent system. Third, every research subject countries classify somatic gene therapy as medicine, therefore it is patentable like existing medicine.

Expressional Modulation of Connexin Isoforms in the Initial Segment of Male Rat treated with Estradiol Benzoate or Flutamide

Lee, Ki-Ho The Korean Society of Developmental Biology 2014 발생과 생식 Vol.18 No.4

Direct cell-cell communication through connexin (Cx) complexes is a way to achieve functional accordance of cells within a tissue or an organ. The initial segment (IS), a part of the epididymis, plays important roles in sperm maturation. Steroid hormones influence on expression of a number of genes in the IS of adult animals. However, developmental effect of sex hormones on the gene expression in the IS has not been examined. In this study, estradiol benzoate (EB, an estrogen agonist) or flutamide (Flu, an androgen antagonist) was exogenously administrated at 1 week of postnatal age, and expressional changes of Cx genes in the IS were determined at 4 months of age by a quantitative real-time PCR analysis. Treatment of EB at $0.015{\mu}g/kg$ body weight (BW) increased expression of Cx30.3, 31.1, and 43 genes. However, treatment of 1.5 mg EB/kg BW resulted in expressional decreases of Cx31, 32, and 45 genes and caused increases of Cx30.3 and 43 gene expression. Significant decreases of Cx31, 31.1, 32, 37, and 45 gene expression were detected with a treatment of $500{\mu}g\;Flu/kg$ BW, while expression of Cx43 gene was significantly increased with a treatment of $500{\mu}g\;Flu/kg$ BW. A treatment of $50{\mu}g\;Flu/kg$ BW led to significant increases of Cx30.3, 32, 37, 40, and 43 gene expression. These findings imply that exogenous exposure of steroidal hormones during the early developmental period would result in aberrant expression of Cx genes in the adult IS.

Expressional Modulation of Connexin Isoforms in the Initial Segment of Male Rat treated with Estradiol Benzoate or Flutamide

Ki-Ho Lee 한국발생생물학회 2014 발생과 생식 Vol.18 No.4

Direct cell-cell communication through connexin (Cx) complexes is a way to achieve functional accordance of cells within a tissue or an organ. The initial segment (IS), a part of the epididymis, plays important roles in sperm maturation. Steroid hormones influence on expression of a number of genes in the IS of adult animals. However, developmental effect of sex hormones on the gene expression in the IS has not been examined. In this study, estradiol benzoate (EB, an estrogen agonist) or flutamide (Flu, an androgen antagonist) was exogenously administrated at 1 week of postnatal age, and expressional changes of Cx genes in the IS were determined at 4 months of age by a quantitative real-time PCR analysis. Treatment of EB at 0.015 mg/kg body weight (BW) increased expression of Cx30.3, 31.1, and 43 genes. However, treatment of 1.5 mg EB/kg BW resulted in expressional decreases of Cx31, 32, and 45 genes and caused increases of Cx30.3 and 43 gene expression. Significant decreases of Cx31, 31.1, 32, 37, and 45 gene expression were detected with a treatment of 500 mg Flu/kg BW, while expression of Cx43 gene was significantly increased with a treatment of 500 mg Flu/kg BW. A treatment of 50 mg Flu/kg BW led to significant increases of Cx30.3, 32, 37, 40, and 43 gene expression. These findings imply that exogenous exposure of steroidal hormones during the early developmental period would result in aberrant expression of Cx genes in the adult IS.

Expressional Modulation of Connexin Isoforms in the Initial Segment of Male Rat treated with Estradiol Benzoate or Flutamide

이기호 한국발생생물학회 2014 발생과 생식 Vol.18 No.4

Direct cell-cell communication through connexin (Cx) complexes is a way to achieve functional accordance ofcells within a tissue or an organ. The initial segment (IS), a part of the epididymis, plays important roles in sperm maturation. Steroid hormones influence on expression of a number of genes in the IS of adult animals. However, developmental effect ofsex hormones on the gene expression in the IS has not been examined. In this study, estradiol benzoate (EB, an estrogenagonist) or flutamide (Flu, an androgen antagonist) was exogenously administrated at 1 week of postnatal age, andexpressional changes of Cx genes in the IS were determined at 4 months of age by a quantitative real-time PCR analysis. Treatment of EB at 0.015 mg/kg body weight (BW) increased expression of Cx30.3, 31.1, and 43 genes. However, treatmentof 1.5 mg EB/kg BW resulted in expressional decreases of Cx31, 32, and 45 genes and caused increases of Cx30.3 and 43 geneexpression. Significant decreases of Cx31, 31.1, 32, 37, and 45 gene expression were detected with a treatment of 500 mgFlu/kg BW, while expression of Cx43 gene was significantly increased with a treatment of 500 mg Flu/kg BW. A treatment of50 mg Flu/kg BW led to significant increases of Cx30.3, 32, 37, 40, and 43 gene expression. These findings imply thatexogenous exposure of steroidal hormones during the early developmental period would result in aberrant expression of Cxgenes in the adult IS.

Exogenous Exposure to Estradiol Benzoate or Flutamide at the Weaning Age Alters Expression of Connexin Isoforms in the Initial Segment of Male Rat

이기호 한국발생생물학회 2015 발생과 생식 Vol.19 No.1

Connexin (Cx) is a complex which allows direct communication between neighboring cells via exchange of signaling molecules and eventually leads to functional harmony of cells in a tissue. The initial segment (IS) is an excurrent duct of male reproductive tract and expression of numerous genes in the IS are controlled by androgens and estrogens. The effects of these steroid hormones on gene expression in the IS during postnatal development have not extensively examined. The present research investigated expressional modulation of Cx isoforms in the IS by exogenous exposure to estrogen agonist, estradiol benzoate (EB), or androgen antagonist, flutamide (Flu), at weaning age. Two different doses of EB or Flu were subcutaneously administrated in 21-day old of male rats, and expressional changes of Cx isoforms in the adult IS were analyzed by quantitative real-time PCR. Treatment of a low-dose EB (0.015 μg/kg body weight) resulted in an increased expression of Cx31 gene and a decreased expression of Cx37 gene. A high-dose EB (1.5 μg/kg body weight) treatment caused an increase of Cx31 gene expression. Increased levels of Cx30.3 and Cx40 transcripts were observed with a low-dose Flu (500 μg/kg body weight) treatment. Treatment of high-dose Flu (50 mg/kg body weight) led to expressional increases of Cx30.3, 40, and 43 genes. Our previous and present findings suggest differential responsiveness on gene expression of Cx isoforms in the IS by androgens and estrogens at different postnatal ages.

Exogenous Exposure to Estradiol Benzoate or Flutamide at the Weaning Age Alters Expression of Connexin Isoforms in the Initial Segment of Male Rat

Lee, Ki-Ho The Korean Society of Developmental Biology 2015 발생과 생식 Vol.19 No.1

Connexin (Cx) is a complex which allows direct communication between neighboring cells via exchange of signaling molecules and eventually leads to functional harmony of cells in a tissue. The initial segment (IS) is an excurrent duct of male reproductive tract and expression of numerous genes in the IS are controlled by androgens and estrogens. The effects of these steroid hormones on gene expression in the IS during postnatal development have not extensively examined. The present research investigated expressional modulation of Cx isoforms in the IS by exogenous exposure to estrogen agonist, estradiol benzoate (EB), or androgen antagonist, flutamide (Flu), at weaning age. Two different doses of EB or Flu were subcutaneously administrated in 21-day old of male rats, and expressional changes of Cx isoforms in the adult IS were analyzed by quantitative real-time PCR. Treatment of a low-dose EB ($0.015{\mu}g/kg$ body weight) resulted in an increased expression of Cx31 gene and a decreased expression of Cx37 gene. A high-dose EB ($1.5{\mu}g/kg$ body weight) treatment caused an increase of Cx31 gene expression. Increased levels of Cx30.3 and Cx40 transcripts were observed with a low-dose Flu ($500{\mu}g/kg$ body weight) treatment. Treatment of high-dose Flu (50 mg/kg body weight) led to expressional increases of Cx30.3, 40, and 43 genes. Our previous and present findings suggest differential responsiveness on gene expression of Cx isoforms in the IS by androgens and estrogens at different postnatal ages.

Exogenous Exposure to Estradiol Benzoate or Flutamide at the Weaning Age Alters Expression of Connexin Isoforms in the Initial Segment of Male Rat

Ki-Ho Lee 한국발생생물학회 2015 발생과 생식 Vol.19 No.1

Connexin (Cx) is a complex which allows direct communication between neighboring cells via exchange of signaling molecules and eventually leads to functional harmony of cells in a tissue. The initial segment (IS) is an excurrent duct of male reproductive tract and expression of numerous genes in the IS are controlled by androgens and estrogens. The effects of these steroid hormones on gene expression in the IS during postnatal development have not extensively examined. The present research investigated expressional modulation of Cx isoforms in the IS by exogenous exposure to estrogen agonist, estradiol benzoate (EB), or androgen antagonist, flutamide (Flu), at weaning age. Two different doses of EB or Flu were subcutaneously administrated in 21-day old of male rats, and expressional changes of Cx isoforms in the adult IS were analyzed by quantitative real-time PCR. Treatment of a low-dose EB (0.015 μg/kg body weight) resulted in an increased expression of Cx31 gene and a decreased expression of Cx37 gene. A high-dose EB (1.5 μg/kg body weight) treatment caused an increase of Cx31 gene expression. Increased levels of Cx30.3 and Cx40 transcripts were observed with a low-dose Flu (500 μg/kg body weight) treatment. Treatment of high-dose Flu (50 mg/kg body weight) led to expressional increases of Cx30.3, 40, and 43 genes. Our previous and present findings suggest differential responsiveness on gene expression of Cx isoforms in the IS by androgens and estrogens at different postnatal ages.

A Role for buttonhead in the Early Head and Trunk Development in the Beetle Tribolium castaneum

Jeon, Haewon,O, Jiyun,Jin, Sil,Lim, Jinsung,Choe, Chong Pyo The Korean Society of Developmental Biology 2019 발생과 생식 Vol.23 No.1

The head gap gene buttonhead (btd) is required for the patterning of head segments in the early Drosophila embryo. Mutant phenotypes of btd display a gap-like phenotype in which antennal, intercalary, mandibular and the anterior portion of the maxillary segments are eliminated. In agreement with the phenotypes, btd is expressed in a stripe covering the head segments at the blastoderm stage. During the early phase of the germband extension, btd is expressed in stripes with single segmental periodicity, which is required for the formation of the peripheral nervous system. In contrast to the key role of btd in Drosophila embryonic development, it has been suggested that Tribolium ortholog of btd (Tc-btd) is dispensable for embryonic head development. In order for better understanding of the requirement of Tc-btd in the early Tribolium embryo, we re-analyzed the expression patterns and functions of Tc-btd during embryonic segmentation. Tc-btd is expressed in segmental stripes at the stages of blastoderm and germband elongation. Up to 28.3% of embryos in which Tc-btd is knocked down displays the loss of antennal, mandibular and the pregnathal regions in the head, with abdominal segments being disrupted in the trunk. Our findings suggest that Tc-btd is required for the head and trunk development in the early Tribolium embryo.

내병성 자포니카 벼 계통 육성과 저항성 유전자 집적효과

김우재,백만기,박현수,이건미,이창민,김석만,조영찬,서정필,정오영,Kim, Woo-Jae,Baek, Man-Kee,Park, Hyeon-Su,Lee, Geon-Mi,Lee, Chang-Min,Kim, Seok-Man,Cho, Young-Chan,Seo, Jeong-Phil,Jeong, O-Young 한국작물학회 2020 한국작물학회지 Vol.65 No.4

This study was carried out to develop a resistant variety against the K3a race of bacterial blight, Xanthomonas oryzae pv. oryzae, through expansion and pyramiding of resistance genes. To develop an elite bacterial blight-resistant cultivar, the breeding process and bacterial blight resistance reactions in advanced backcross lines (ABLs) were analyzed. ABLs21 which contain Xa3 and Xa21, were developed by double backcrossing japonica cultivar Hwanggeumnuri, which has bacterial blight resistant Xa3 gene, and indica variety IRBB21, which havs Xa21 gene, followed by disease resistance bioassay and marker-assisted selection. The resistance genes of ABLs21 were amplified by PCR with the molecular markers 9643.T4 (Xa3) and U1/I1 (Xa21). Hwanggeumnuri and IRBB3 showed resistance reactions against K1, K2, and K3 races, and a susceptible reaction against K3a, K4, and K5 races. IRBB21 showed resistance reactions against K2, K3, K3a, K4 and K5 races, and a susceptible reaction against K1 race. Hwanggeumnuri showed susceptible reactions at the seedling, tillering and adult stages (all stages), whereas ABL21-1 showed moderate resistance at the tillering stage. ABL21-1 showed stable resistance against 18 isolates of K3a race, and the lesion length was shorter than that of the donor parents. In cluster analysis, the HB4032 isolate showed the highest pathogenicity among the 18 isolates. The molecular marker polymorphisms and average substituted chromosome segment lengths of ABLs21 were 63.2 % and 86.1 cM, respectively. Insertion of the donor chromosomal segments occurred in the predicted region of the Xa21 gene of ABLs21.

A Role for buttonhead in the Early Head and Trunk Development in the Beetle Tribolium castaneum

전해원,오지윤,진실,임진성,최종표 한국발생생물학회 2019 발생과 생식 Vol.23 No.1

The head gap gene buttonhead (btd) is required for the patterning of head segments in the early Drosophila embryo. Mutant phenotypes of btd display a gap-like phenotype in which antennal, intercalary, mandibular and the anterior portion of the maxillary segments are eliminated. In agreement with the phenotypes, btd is expressed in a stripe covering the head segments at the blastoderm stage. During the early phase of the germband extension, btd is expressed in stripes with single segmental periodicity, which is required for the formation of the peripheral nervous system. In contrast to the key role of btd in Drosophila embryonic development, it has been suggested that Tribolium ortholog of btd (Tc-btd) is dispensable for embryonic head development. In order for better understanding of the requirement of Tc-btd in the early Tribolium embryo, we re-analyzed the expression patterns and functions of Tc-btd during embryonic segmentation. Tc-btd is expressed in segmental stripes at the stages of blastoderm and germband elongation. Up to 28.3% of embryos in which Tc-btd is knocked down displays the loss of antennal, mandibular and the pregnathal regions in the head, with abdominal segments being disrupted in the trunk. Our findings suggest that Tc-btd is required for the head and trunk development in the early Tribolium embryo.