JP2020512010A - 自己免疫疾患及び糖尿病を治療するウイルスベクター、その構築方法及び応用 - Google Patents
自己免疫疾患及び糖尿病を治療するウイルスベクター、その構築方法及び応用 Download PDFInfo
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Abstract
Description
t−1−R:5´−CAACCGGAATTCTCATCACTTGGCCT−3´を
設計してPCR増幅を行い、得られた前記mfat−1遺伝子配列の両端にNheI及びEcoRI酵素消化部位を持たせるステップ(1)と、
ステップ(1)で得られたPCR増幅産物を電気泳動し、次に、ゲルを切り出して回収して精製し、得られたPCR増幅産物を制限エンドヌクレアーゼNheI及びEcoRで酵素消化して使用時まで保存し、空の前記レンチウイルス発現プラスミド又はアデノ随伴ウイルス発現プラスミドを制限エンドヌクレアーゼNheI及びEcoRで酵素消化して、使用時まで保存するステップ(2)と、
ステップ(2)で得られたDNA断片を酵素消化後の前記空のシャトルプラスミドに連結して、ウイルスベクターを得るステップ(3)とを含む。
5×PrimeSTAR(登録商標)Buffer(Mg2+plus) 10μlと、
dNTP Mixture(各dNTP 2.5mM) 4μlと、
テンプレートDNA 20−200ngと、
上流プライマーmfat−1−F(10μM) 1μlと、
下流プライマーmfat−1−R(10μM) 1μlと、
PrimeSTA(登録商標)HS DNA Polymerase(2.5U/μl) 0.5μlと、
50μLまで補充する滅菌超純水とを含む。
と、下流プライマーmfat−1−R:5´−CAACCGGAATTCTCATCA
CTTGGCCT−3´を設計し、mfat−1領域をPCR増幅して、その配列の両
端にNheI及びEcoRI酵素消化部位を持たせた。
<110>広州華真生物医薬科技有限公司
<120>自己免疫疾患及び糖尿病を治療するウイルスベクター、その構築方法及び応用
<130> SG151016001
<160> 1
<170> Patentln version 3.3
<210> 1
<211> 1248
<212> DNA
<213> mfat−1
<400> 1
ctagaatcgt cgacctgcag gcatggtcgc ccacagcagc gagggcctga gcgccaccgc 60
ccctgtgaca ggcggcgacg tgctggtcga cgccagagcc agcctggagg agaaggaggc 120
ccccagggac gtcaacgcca acaccaagca ggccaccacc gaggagccca gaatccagct 180
gcccaccgtg gacgccttcc ggagagccat ccccgcccac tgcttcgagc gggacctggt 240
gaagagcatc cgctacctgg tgcaggactt cgccgccctg accatcctgt acttcgccct 300
cccgccttc gagtacttcg gcctgttcgg ctatctggtg tggaacatct tcatgggcgt 360
gttcggcttc gccctgttcg tggtgggcca cgactgcctg cacggcagct tcagcgacaa 420
ccagaacctg aacgacttca tcggccacat cgccttcagc cccctgttca gcccctactt 480
cccctggcag aagagccaca agctgcacca cgccttcacc aaccacatcg acaaggacca 540
cggccatgtg tggattcagg acaaggactg ggaggccatg cccagctgga agcggtggtt 600
caaccccatc cccttcagcg gctggctgaa gtggttcccc gtgtataccc tgtttggctt 660
ctgcgacggc agccacttct ggccttacag cagcctgttt gtgcggaaca gcgaaagagt 720
gcagtgcgtc atcagcggca tctgctgctg tgtgtgcgcc tacatcgccc tgacaatcgc 780
cggcagctac agcaactggt tctggtacta ctgggtgccc ctgagcttct tcggcctgat 840
gctggtgatc gtgacctacc tgcagcacgt ggacgacgtg gccgaagtgt acgaggccga 900
cgagtggagc tttgtgcggg gccagaccca gaccatcgac cggtactacg gcctgggcct 960
ggacaccacc atgcaccaca tcaccgacgg acacgtggcc catcactttt tcaacaagat 1020
cccccactac cacctgatcg aggccaccga gggcgtgaag aaagtgctgg agcccctgag 1080
cgacacccag tacggctaca agagccaggt gaactacgac ttcttcgccc ggttcctgtg 1140
gttcaactac aagctggact atctggtgca caagaccgcc ggcatcatgc agttccggac 1200
caccctggag gaaaaggcca aggccaagtg atgaatgcaa gctggcgt 1248
Claims (15)
- ウイルスベクターであって、
mfat−1遺伝子がクローニングされたレンチウイルス発現プラスミド又はmfat−1遺伝子がクローニングされたアデノ随伴ウイルス発現プラスミドであり、
前記mfat−1遺伝子は、SEQ ID No.:1に示されることを特徴とするウイルスベクター。 - 前記レンチウイルス発現プラスミドは、pLJM1−CMV−hPGK−EGFPプラスミド、pLJM1−CMV−hPGK−mkate2プラスミド、pLenti−CMV−MCS−GFP−SV−puroプラスミド、FUGW、pLenti−puro、pLenti−MP2又はpLentiプラスミドであり、前記アデノ随伴ウイルス発現プラスミドは、pEMBL−AAV−D(+)−CMV−eGFP−SV40プラスミド、AAV GFPプラスミド、AAV1プラスミド、AAV2プラスミド、rAAV2プラスミド、AAV5プラスミド、AAV8プラスミド、AAV9プラスミド又はpAV−FH AAVプラスミドであることを特徴とする請求項1に記載のウイルスベクター。
- 請求項1又は2に記載のウイルスベクターの構築方法であって、
前記mfat−1遺伝子をレンチウイルス発現プラスミド又はアデノ随伴ウイルス発現プラスミドにクローニングして、ウイルスベクターを得ることを特徴とする構築方法。 - 前記mfat−1遺伝子配列をテンプレートとして、プライマーmfat−1−F:5´−TATTAAGCTAGCATGGTCGCCCACAGCA−3´と、mfa
t−1−R:5´−CAACCGGAATTCTCATCACTTGGCCT−3´を
設計してPCR増幅を行い、得られた前記mfat−1遺伝子配列の両端にNheI及びEcoRI酵素消化部位を持たせるステップ(1)と、
ステップ(1)で得られたPCR増幅産物を電気泳動し、次に、ゲルを切り出して回収して精製し、得られたPCR増幅産物を制限エンドヌクレアーゼNheI及びEcoRで酵素消化して使用時まで保存し、空の前記レンチウイルス発現プラスミド又はアデノ随伴ウイルス発現プラスミドを制限エンドヌクレアーゼNheI及びEcoRで酵素消化して、使用時まで保存するステップ(2)と、
ステップ(2)で得られたDNA断片を酵素消化後の前記空のシャトルプラスミドに連結して、ウイルスベクターを得るステップ(3)とを含むことを特徴とする請求項3に記載のウイルスベクターの構築方法。 - 前記ステップ(1)におけるPCR増幅反応系は、
5×PrimeSTAR(登録商標)Buffer(Mg2+plus) 10μlと、
dNTP Mixture(各dNTP 2.5mM) 4μlと、
テンプレートDNA 20−200ngと、
上流プライマーmfat−1−F(10μM)1μlと、
下流プライマーmfat−1−R(10μM)1μlと、
PrimeSTAR(登録商標)HS DNA Polymerase(2.5U/μl)0.5μlと、
50μLまで補充する滅菌超純水とを含むことを特徴とする請求項3又は4に記載のウイルスベクターの構築方法。 - 前記ステップ(1)におけるPCR増幅反応の過程において、98℃で5分変性し、98℃で10秒保持して、60℃で15秒保持し、72℃で2分保持することを合計30回サイクルし、最後に、72℃で10分伸長することを特徴とする請求項3又は4に記載のウイルスベクターの構築方法。
- 組換えウイルスベクターであって、
請求項1又は2に記載のウイルスベクターを用いて構築されることを特徴とする組換えウイルスベクター。 - ウイルス粒子であって、
請求項1又は2に記載の前記ウイルスベクターを細胞に形質転換して得るウイルス粒子であることを特徴とするウイルス粒子。 - 前記ウイルス粒子の投与方式は、静脈注射であることを特徴とする請求項8に記載のウイルス粒子。
- 請求項1又は2に記載のウイルスベクター、又は請求項7に記載の組換えウイルスベクター、又は請求項8に記載のウイルス粒子の、糖尿病治療薬又は自己免疫関連疾患治療薬の調製における応用
- 前記糖尿病は、自己免疫性1型糖尿病であることを特徴とする請求項10に記載の応用。
- 前記自己免疫関連疾患は、Th細胞分化のアンバランス及びその分泌サイトカインのアンバランスによる自己免疫疾患であることを特徴とする請求項10に記載の応用。
- 前記自己免疫疾患は、1型糖尿病、多発性硬化症、関節リウマチ及び全身性エリテマトーデスであることを特徴とする請求項12に記載の応用。
- 医薬品であって、
請求項1又は2に記載のウイルスベクター、又は請求項7に記載の組換えウイルスベクター、又は請求項8に記載のウイルス粒子と、その薬学的に許容可能な担体とを含むことを特徴とする医薬品。 - 一般的なプロセスに従って、請求項1又は2に記載のウイルスベクター、又は請求項7に記載の組換えウイルスベクター、又は請求項8に記載のウイルス粒子に一般的な佐剤を添加して、臨床的に許容可能な剤形に調製することを特徴とする請求項14に記載の医薬品。
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JP2007527711A (ja) * | 2004-02-04 | 2007-10-04 | ザ・ジェネラル・ホスピタル・コーポレイション | 生物学的細胞における多価不飽和脂肪酸の含有量を変更するための組成物および方法 |
CN103074347A (zh) * | 2013-01-23 | 2013-05-01 | 南京华贞生物医药科技有限公司 | 适用于哺乳动物表达的人源化mfat1基因及其应用 |
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WO2009073618A2 (en) * | 2007-11-30 | 2009-06-11 | New York Medical College | Compositions comprising hdac inhibitors and methods of their use in restoring stem cell function and preventing heart failure |
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US10182560B2 (en) * | 2014-03-21 | 2019-01-22 | The General Hospital Corporation | Transgene construct encoding delta 12 fatty acid |
CN106591370A (zh) * | 2015-10-19 | 2017-04-26 | 南京华贞生物医药科技有限公司 | 一种治疗自身免疫性相关疾病以及糖尿病的病毒载体及其构建方法和应用 |
CN111500636B (zh) * | 2017-04-01 | 2024-04-26 | 广州华真医药科技有限公司 | 治疗自身免疫性相关疾病的病毒载体及其构建方法和应用 |
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ZA201906218B (en) | 2021-03-31 |
CA3056691C (en) | 2023-06-27 |
AU2018241658A1 (en) | 2019-10-10 |
EP3608414A4 (en) | 2021-01-27 |
KR20190135516A (ko) | 2019-12-06 |
CA3056691A1 (en) | 2018-10-04 |
CN107119074B (zh) | 2020-06-19 |
KR102383866B1 (ko) | 2022-04-06 |
CN111500636B (zh) | 2024-04-26 |
WO2018177376A1 (zh) | 2018-10-04 |
CN107119074A (zh) | 2017-09-01 |
US20210269824A1 (en) | 2021-09-02 |
CN111500636A (zh) | 2020-08-07 |
AU2022200653A1 (en) | 2022-02-24 |
EP3608414A1 (en) | 2020-02-12 |
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