{"id":1848,"date":"2018-09-25T13:33:23","date_gmt":"2018-09-25T04:33:23","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=1848"},"modified":"2018-09-29T10:35:04","modified_gmt":"2018-09-29T01:35:04","slug":"%eb%af%b8%ed%86%a0%ec%bd%98%eb%93%9c%eb%a6%ac%ec%95%84-dna-%ec%9c%a0%ec%a0%84%ec%9e%90%ed%8e%b8%ec%a7%91-%ea%b4%80%eb%a0%a8-%eb%85%bc%eb%ac%b8-2%ed%8e%b8","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=1848","title":{"rendered":"\ubbf8\ud1a0\ucf58\ub4dc\ub9ac\uc544 DNA \uc720\uc804\uc790\ud3b8\uc9d1 \uad00\ub828 \ub17c\ubb38 2\ud3b8 & \uc720\uc804\uc790 \uac00\uc704\ub85c \u2018\ub9d0\ub77c\ub9ac\uc544 \ubaa8\uae30\u2019 \uc808\uba78"},"content":{"rendered":"

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Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo<\/h5>\n

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\uc5ec\uae30<\/u><\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~<\/p>\n

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Abstract<\/h6>\n
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Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNAAla<\/sup>\u00a0mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin.<\/p>\n<\/div>\n

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MitoTALEN reduces mutant mtDNA load and restores tRNAAla<\/sup>\u00a0levels in a mouse model of heteroplasmic mtDNA mutation<\/h5>\n

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\uc5ec\uae30<\/u><\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~<\/p>\n

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Abstract<\/h6>\n
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Mutations in the mitochondrial DNA (mtDNA) are responsible for several metabolic disorders, commonly involving muscle and the central nervous system1<\/a><\/sup>. Because of the critical role of mtDNA in oxidative phosphorylation, the majority of pathogenic mtDNA mutations are heteroplasmic, co-existing with wild-type molecules1<\/a><\/sup>. Using a mouse model with a heteroplasmic mtDNA mutation2<\/a><\/sup>, we tested whether mitochondrial-targeted TALENs (mitoTALENs)3<\/a>,4<\/a><\/sup>\u00a0could reduce the mutant mtDNA load in muscle and heart. AAV9-mitoTALEN was administered via intramuscular, intravenous, and intraperitoneal injections. Muscle and heart were efficiently transduced and showed a robust reduction in mutant mtDNA, which was stable over time. The molecular defect, namely a decrease in transfer RNAAla<\/sup>\u00a0levels, was restored by the treatment. These results showed that mitoTALENs, when expressed in affected tissues, could revert disease-related phenotypes in mice.<\/p>\n<\/div>\n

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http:\/\/nownews.seoul.co.kr\/news\/newsView.php?id=20180928601011&wlog_tag3=naver<\/p>\n

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\uc720\uc804\uc790 \uac00\uc704\ub85c \u2018\ub9d0\ub77c\ub9ac\uc544 \ubaa8\uae30\u2019 \uc808\uba78\u2026\u82f1 \uc5f0\uad6c\uc9c4 \uc2e4\ud5d8 \uc131\uacf5<\/h5>\n

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\uc720\uc804\uc790 \uac00\uc704\ub85c \u2018\ub9d0\ub77c\ub9ac\uc544 \ubaa8\uae30\u2019 \uc808\uba78\u2026\u82f1 \uc5f0\uad6c\uc9c4 \uc2e4\ud5d8 \uc131\uacf5<\/em><\/span><\/p>\n

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\uc601\uad6d \uc784\ud398\ub9ac\uc5bc\uce7c\ub9ac\uc9c0\ub7f0\ub358 \uc5f0\uad6c\uc9c4\uc740 \u2018\ud06c\ub9ac\uc2a4\ud37c \uce90\uc2a49\u2019(CRISPR<\/span>–Cas<\/span>9)\uc73c\ub85c \ubd88\ub9ac\ub294 \uc720\uc804\uc790 \uac00\uc704 \uae30\uc220\ub85c \ub9cc\ub4e0 \u2018\ubd88\uc784 \ubaa8\uae30\u2019\ub97c \uc774\uc6a9\ud55c \uc2e4\ub0b4 \uc2e4\ud5d8\uc5d0\uc11c \ub9d0\ub77c\ub9ac\uc544 \ubaa8\uae30\ub97c \uc808\uba78\ud558\ub294 \ub370 \uc131\uacf5\ud588\ub2e4\uace0 \uad6d\uc81c\ud559\uc220\uc9c0 \u2018\ub124\uc774\ucc98 \ubc14\uc774\uc624\ud14c\ud06c\ub180\ub85c\uc9c0\u2019(Nature<\/span>\u00a0Biotechnology<\/span>) \ucd5c\uc2e0\ud638\uc5d0 \ubc1c\ud45c\ud588\ub2e4.<\/p>\n

\uc5f0\uad6c\uc9c4\uc740 \uc774\ubc88 \uc5f0\uad6c\uc5d0\uc11c \ub9d0\ub77c\ub9ac\uc544 \ub9e4\uac1c \ubaa8\uae30\uc778 \uc544\ub178\ud3a0\ub9ac\uc2a4 \uac10\ube44\uc544\uc758 \uc624\ub7ab\ub3d9\uc548 \uc774\uc5b4\uc838\uc628 \ucd08\uc720\uc804\uc790(supergene<\/span>)\ub97c \uc870\uc791\ud574 \uc138\ub300\ub97c \uac70\ub4ed\ud560\uc218\ub85d \ud761\ud608\uacfc \ubc88\uc2dd\uc774 \ubd88\uac00\ub2a5\ud55c \uc554\ubaa8\uae30 \uc218\ub97c \uae09\uaca9\ud788 \ub298\ub9ac\uace0\uc790 \ud588\ub2e4.<\/p>\n

\uc989 \ud761\ud608\uacfc \ubc88\uc2dd\uc744 \ubd88\uac00\ub2a5\ud558\uac8c \ud558\ub294 \ud2b9\uc815 \ud615\uc9c8\uc744 \ub2e4\uc74c \uc138\ub300\uc5d0 \ube60\ub974\uac8c \uc804\ub2ec\ud558\ub294 \uac83\uc774\ub2e4.<\/p>\n

\uc774\ub978\ubc14 \u2018\uc720\uc804\uc790 \ub4dc\ub77c\uc774\ube0c\u2019\ub85c\ub3c4 \ubd88\ub9ac\ub294 \uc774 \uae30\uc220\uc740 \ud2b9\uc815\ud55c \uc720\uc804 \ud615\uc9c8\uc774 \ud6c4\uc138\uc5d0 \uc120\ud0dd\uc801\uc73c\ub85c \ube60\ub974\uac8c \ud37c\uc9c8 \uc218 \uc788\ub3c4\ub85d \uc0dd\ubb3c \uc885 \uc5fc\uc0c9\uccb4(DNA<\/span>) \ub0b4\uc5d0 \uc720\uc804\uc790 \uac00\uc704\ub97c \uc2ec\uc5b4 \uc9c0\uad6c \uc804\uccb4\uc758 \uc720\uc804\uc790 \uad6c\uc131\uc744 \ubc14\uafc0 \uc218 \uc788\ub294 \ud575\uc2ec \uc0dd\uba85\uacf5\ud559 \uae30\uc220\uc774\ub2e4.<\/p>\n

\uc5f0\uad6c\uc9c4\uc5d0 \ub530\ub974\uba74, \uc774\ubc88 \uc2e4\ud5d8\uc5d0\uc11c\ub294 \ubd88\uacfc 8\uc138\ub300 \ub9cc\uc5d0 \ub9d0\ub77c\ub9ac\uc544 \uc554\ubaa8\uae30\uac00 \uc644\uc804\ud788 \uc0ac\ub77c\uc84c\ub2e4. \uc774\uc5d0 \ub530\ub77c \uc790\uc190\uc744 \ub0a8\uae38 \uc218 \uc5c6\uac8c \ub3fc \uac1c\uccb4\uad70\uc740 \uc644\uc804\ud788 \ubd95\uad34\ud558\uace0 \ub9d0\uc558\ub2e4.<\/p>\n

\uc5f0\uad6c\ub97c \uc774\ub048 \uc548\ub4dc\ub808\uc544 \ud06c\ub9ac\uc0b0\ud2f0 \uc0dd\uba85\uacfc\ud559\ubd80 \uad50\uc218\ub294 \u201c\uc720\uc804\uc790 \ub4dc\ub77c\uc774\ube0c\uac00 \uc6b0\ub9ac \ubaa9\uc801\ub300\ub85c \uae30\ub2a5\ud574 \uc9c0\ub09c \uba87 \uc138\uae30 \ub3d9\uc548 \uc778\ub958\ub97c \uad34\ub86d\ud574\uc628 \uc9c8\ubcd1\uacfc\uc758 \uc2f8\uc6c0\uc5d0\uc11c \ud76c\ub9dd\uc744 \ucc3e\uc744 \uc218 \uc788\uc5c8\ub2e4\u201d\uace0 \ub9d0\ud588\ub2e4.<\/p>\n

\ub9d0\ub77c\ub9ac\uc544 \uac10\uc5fc\uc790 \uc218\ub294 \uc9c0\ub09c 2016\ub144 \uae30\uc900\uc73c\ub85c \uc804 \uc138\uacc4 2\uc5b5 \uba85 \uc774\uc0c1\uc73c\ub85c, \uc0ac\ub9dd\uc790\ub294 45\ub9cc \uba85\uc5d0 \ub2ec\ud55c\ub2e4. \uc9c0\uad6c\uc0c1\uc5d0\uc11c \uc0ac\ub9dd\ub960\uc774 \uac00\uc7a5 \ub192\uc740 \uac10\uc5fc \uc9c8\ud658 \uc911 \ud558\ub098\ub85c \uaf3d\ud78c\ub2e4.<\/p>\n

\ubb3c\ub860 \uc720\uc804\uc790 \ub4dc\ub77c\uc774\ube0c \uae30\uc220\uc744 \uc774\uc6a9\ud55c \uc2e4\ub0b4 \uc2e4\ud5d8\uc740 \uc774\ubc88 \uc5f0\uad6c\uc9c4 \uc678\uc5d0\ub3c4 \ub2e4\ub978 \uc5f0\uad6c\uc9c4\ub4e4 \uc5ed\uc2dc \uc9c4\ud589\ud574 \uc654\uc9c0\ub9cc, \uc800\ud56d\uc131 \ub3cc\uc5f0\ubcc0\uc774\uc758 \ucd9c\ud604\uc73c\ub85c \uc9c0\uae08\uae4c\uc9c0 \uc2e4\ud5d8\uc5d0 \uc131\uacf5\ud55c \uc801\uc740 \uc5c6\uc5c8\ub2e4.<\/p>\n

\uc774\uc5d0 \ub300\ud574 \ud06c\ub9ac\uc0b0\ud2f0 \uad50\uc218\ub294 \u201c\uc774\uc81c \uc6b0\ub9ac\ub294 \ub2e4\uc74c \ub2e8\uacc4\ub85c \uc5f4\ub300 \ud658\uacbd\uc744 \uc7ac\ud604\ud55c \ud3d0\uc1e0\uc801\uc778 \uc2e4\ud5d8\uc2e4 \ud658\uacbd\uc5d0\uc11c \uc720\uc804\uc790 \ub4dc\ub77c\uc774\ube0c \uae30\uc220\uc744 \uc2dc\ud5d8\ud560 \uacc4\ud68d\u201d\uc774\ub77c\uba74\uc11c\ub3c4 \u201c\uc790\uc5f0 \ud658\uacbd\uc5d0\uc11c\uc758 \uc2e4\ud5d8\uc744 \uac80\ud1a0\ud558\ub824\uba74 \uc801\uc5b4\ub3c4 5~10\ub144\uc774 \uc9c0\ub098\uc57c \ud560 \uac83\u201d\uc774\ub77c\uace0 \uc9c0\uc801\ud588\ub2e4.<\/p>\n

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\uc0ac\uc9c4=\ub124\uc774\ucc98 \ubc14\uc774\uc624\ud14c\ud06c\ub180\ub85c\uc9c0<\/p>\n

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 <\/p>\n","protected":false},"excerpt":{"rendered":"

    Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo   \uc5ec\uae30\ub97c \ud074\ub9ad\ud558\uc138\uc694~   Abstract Mutations of the mitochondrial genome (mtDNA) underlie(more…)<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_feature_clip_id":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[33,29,30],"tags":[],"class_list":["post-1848","post","type-post","status-publish","format-standard","hentry","category-do-biology","category-lets-do-science","category-recent-science-news"],"aioseo_notices":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack-related-posts":[{"id":2529,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2529","url_meta":{"origin":1848,"position":0},"title":"Mitochondrial DNA can be inherited from fathers, not just mothers","author":"biochemistry","date":"January 18, 2019","format":false,"excerpt":"\u00a0 \u00a0 A tenet of elementary biology is that mitochondria \u2014 the cell\u2019s powerhouses \u2014 and their DNA are inherited exclusively from mothers. A provocative study suggests that fathers also occasionally contribute. \u00a0 The DNA of eukaryotic organisms (such as animals, plants and fungi) is stored in two cellular compartments:\u2026","rel":"","context":"In "Let's Do Biology!"","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3625,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3625","url_meta":{"origin":1848,"position":1},"title":"Principles of and strategies for germline gene therapy","author":"biochemistry","date":"June 4, 2019","format":false,"excerpt":"\u00a0 \u00a0 Abstract Monogenic disorders occur at a high frequency in human populations and are commonly inherited through the germline. Unfortunately, once the mutation has been transmitted to a child, only limited treatment options are available in most cases. However, means of correcting disease-causing nuclear and mitochondrial DNA mutations in\u2026","rel":"","context":"In "Let's Do Biology!"","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4921,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4921","url_meta":{"origin":1848,"position":2},"title":"Mitochondrial DNA promotes autoimmunity","author":"biochemistry","date":"January 7, 2020","format":false,"excerpt":"\u00a0 \u00a0 The immune system provides essential protection from microbial infection but can damage tissue when its functions are excessive, sustained, or insufficiently regulated. In autoimmune disease, T lymphocytes and autoantibodies (antibodies directed to \u201cself\u201d-antigens) target the immune response to host tissue. But innate immunity, the first response to infection\u2026","rel":"","context":"In "Let's Do Biology!"","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2234,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2234","url_meta":{"origin":1848,"position":3},"title":"Not Your Mom\u2019s Genes: Mitochondrial DNA Can Come from Dad","author":"biochemistry","date":"December 3, 2018","format":false,"excerpt":"\u00a0 \u00a0 A new study provides compelling evidence that children can inherit mitochondrial DNA from both their parents. \u00a0 A new study shows that, in contrast to a longstanding rule in human biology, mitochondrial DNA can be inherited from fathers as well as mothers. Photo Credit: seal1837, Pixabay \u00a0 The\u2026","rel":"","context":"In "Let's Do Biology!"","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/163.180.4.222\/lab\/wp-content\/uploads\/2018\/12\/baby-2436661_1920.width-2500-300x169.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":2252,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2252","url_meta":{"origin":1848,"position":4},"title":"The paradox of mutations and cancer","author":"biochemistry","date":"December 3, 2018","format":false,"excerpt":"\u00a0 \u00a0 The past decade has witnessed the cataloging of genetic mutations in cancer genomes, providing new insights into how and in what ways cancer can develop and spread (1,\u00a02). The focus has been on defining specific \u201cdriver\u201d mutations, genetic errors in cancer cells that reveal basic biological processes gone\u2026","rel":"","context":"In "Essays on Science"","block_context":{"text":"Essays on Science","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=32"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2952,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2952","url_meta":{"origin":1848,"position":5},"title":"The CRISPR \ufefffix that could combat inherited blood disorders","author":"biochemistry","date":"March 27, 2019","format":false,"excerpt":"\u00a0 Researchers have finally identified a reliable way to edit the genes of blood stem cells. \u00a0 The elongated red blood cells of people with sickle-cell disease can block small blood vessels, reducing the flow of oxygen to nearby tissues. Credit: Eye of Science\/SPL \u00a0 \u00a0 \u00a0 An enhanced version\u2026","rel":"","context":"In "Let's Do Biology!"","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"jetpack_sharing_enabled":false,"jetpack_shortlink":"https:\/\/wp.me\/p9Xo1j-tO","_links":{"self":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/1848","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1848"}],"version-history":[{"count":4,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/1848\/revisions"}],"predecessor-version":[{"id":1925,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/1848\/revisions\/1925"}],"wp:attachment":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1848"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1848"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1848"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}