᪩✄⏣኱Ꮫ኱Ꮫ㝔 ๰㐀⌮ᕤᏛ◊✲⛉ ༤㻌 ኈ㻌 ㄽ㻌 ᩥ㻌 ᴫ㻌せ ㄽ ᩥ 㢟 ┠ Fabrication of DNA / Apatite Nano-composite Layer for Gene Transfer 㑇ఏᏊᑟධࡢࡓࡵࡢ DNA /࢔ࣃࢱ࢖ࢺ ࢼࣀ」ྜᒙࡢタィᵓ⠏࡟㛵ࡍࡿ◊✲ ⏦ ㄳ ⪅ Yushin YAZAKI ▮ᓮ ౡ᣺ 2013 ᖺ 5 ᭶ ㏆ ᖺ ࠊࠕ ⣽ ⬊ ࠖࠊࠕ ቑ Ṫ ࣭ ศ ໬ ᅉ Ꮚ ࠖࠊࠕ ㊊ ሙ 㸦 ࢫ ࢟ ࣕ ࣍ ࣮ ࣝ ࢻ 㸧ࠖ ࢆ 㐺 ษ ࡟ ⤌ ࡳྜࢃࡏࠊᶵ⬟ࡉࡏࡿࡇ࡜࡟ࡼࡗ࡚ࠊ⑓Ẽࡸ஦ᨾ࡞࡝࡟ࡼࡾኻࢃࢀࡓ⮚ჾࡸ⤌⧊ ࡢᶵ⬟ࢆᅇ᚟ࡉࡏࡼ࠺࡜࠸࠺෌⏕་⒪ࡀὀ┠ࡉࢀ࡚࠸ࡿࠋࡑࡢ㝿ࠊ⤌⧊ࡸ⮚ჾࡢ ෌⏕ࠊཬࡧᶵ⬟ᅇ᚟ࡢࡓࡵ࡟ࡣࠊᖿ⣽⬊ࡢቑṪࠊศ໬ࢆไᚚࡍࡿᚲせࡀ࠶ࡿࠋࡑ ࡢࡓࡵࡢᡭἲࡢ୍ࡘ࡜ࡋ࡚㑇ఏᏊᑟධࡀᣲࡆࡽࢀࡿࠋᚑ᮶ࡢ㑇ఏᏊᑟධἲࡣ୍⯡ ࡟ࠊDNA ࡜㑇ఏᏊᑟධ๣ࡢ」ྜ⢏Ꮚࢆ⣽⬊ࡀᏑᅾࡍࡿᇵ㣴ᾮࡸ⏕యෆ➼ࡢ⁐ᾮ ┦୰࡟ศᩓࡉࡏࡿᡭ㡰࡛⾜ࢃࢀࡿࠋࡋ࠿ࡋࡇࡢࡼ࠺࡞ᡭἲ࡛ࡣ㸪ᾮ┦୰࡟࠾ࡅࡿ ⢏Ꮚࡢືែไᚚࡀᅔ㞴࡞ࡓࡵ㸪㑇ఏᏊࢆᑟධࡍࡿሙᡤ㸦఩⨨㸧ࢆࢥࣥࢺ࣮ࣟࣝࡍ ࡿࡇ࡜ࡣ㞴ࡋ࠸ࠋࡋࡓࡀࡗ࡚ࠊ≉࡟ in vivo ᛂ⏝࡟࠾࠸࡚ࡣ㸪⢏Ꮚࡢᣑᩓ࡟ ࡼࡿ἞⒪ຠᯝࡢపῶࡸ๪స⏝㸦౛࠼ࡤࠊ㠀ᶆⓗ⣽⬊࡬ࡢ㑇ఏᏊᑟධࡸ㸪⫢⮚ࡸ⫵ ࡞࡝࡬ࡢᑟධ๣ࡢ⵳✚࡟ࡼࡿ㞀ᐖ㸧ࡀᠱᛕࡉࢀࡿࠋྠᵝ࡟⢏Ꮚࡢືែไᚚࡀᅔ㞴ఏ ࡞ࡇ࡜࡟㉳ᅉࡋ࡚ࠊ㑇Ꮚࡀ⣽⬊࡟ᑟධࡉࢀࡿࢱ࢖࣑ࣥࢢࡢไᚚࠊ⏕యෆࡢᵝ࡟」 ᩘࡢ⣽⬊✀ࡀᏑᅾࡍࡿ⣔࡟࠾ࡅࡿ≉ᐃࡢ✀㢮ࡢ⣽⬊ࡢࡳ࡬ࡢ㑇ఏᏊᑟධ࡞࡝ࡶᅔ 㞴࡛࠶ࡿࠋ୍᪉ࠊࣁ࢖ࢻࣟ࢖࢟ࢩ࢔ࣃࢱࢺ࡟௦⾲ࡉࢀࡿࣜࣥ㓟࢝ࣝࢩ࣒࢘ࡣࣂ࢖ ࢜ࢭ࣑ࣛࢵࢡࢫ࡜ࡋ࡚ᗈࡃ▱ࡽࢀࠊ⏕యᮦᩱᏛ࡜⮫ᗋ་Ꮫ㸦≉࡟ᩚᙧእ⛉ࡸṑ⛉ 㸧ࡢ㡿ᇦ࡛⮫ᗋᛂ⏝ࡉࢀ࡚ࡁࡓࠋ௚᪉ࠊศᏊ⏕≀Ꮫࡢศ㔝࡛ࡣࠊࣜࣥ㓟࢝ࣝࢩ࢘ ࣒ࡣ㠀࢘࢖ࣝࢫ⣔㑇ఏᏊᑟධ๣࡜ࡋ࡚㛗ࡃ⏝࠸ࡽࢀ࡚ࡁࡓࠋ1990 ᖺ௦࡟ධࡾ ෌⏕་⒪ࡀὀ┠ࡉࢀࠊୖグࡢྛศ㔝࡛ࡶ෌⏕་⒪ᛂ⏝࡟ྥࡅࡓ◊✲ࡀ㐍ࡵࡽࢀጞ ࡵࡓࠋ౛࠼ࡤ㏆ᖺࠊࣜࣥ㓟࢝ࣝࢩ࣒࢘⣔ᮦᩱࡢ◊✲ࡀ⤌ࡳྜࢃࡉࢀࠊDNA ࡀࢼ ࣀࢫࢣ࣮࡛ࣝࣜࣥ㓟࢝ࣝࢩ࣒࢘࡟ᢸᣢࡉࢀࡓ」ྜᒙ㸦௨ୗࠊD-CaP ᒙ㸧ࡀ㛤 Ⓨࡉࢀࡓࠋࡇࡢ」ྜᒙࡣࣂ࢖࢜ࢭ࣑ࣛࢵࢡࢫཬࡧ㑇ఏᏊᑟධ๣ࡢ୧⪅ࡢᶵ⬟ࢆే ࡏᣢࡘࠋࡍ࡞ࢃࡕࠊ㧗࠸⏕య㐺ྜᛶ࡜ࠊᮦᩱ⾲㠃࡟ࡼࡗ࡚፹௓ࡉࢀࡿ㑇ఏᏊᑟධ ᶵ⬟ࢆ᭷ࡍࡿࠋࡶࡋࠊࡇࡢ D-CaP ᒙ࡟ㄢ㢟࡛࠶ࡿ㑇ఏᏊᑟධࡢሙᡤࡸ᫬ᮇࡢ ࢥࣥࢺ࣮ࣟࣝ⬟ࠊ࠶ࡿ࠸ࡣ≉ᐃ✀ࡢ⣽⬊㸦ᶆⓗ⣽⬊㸧ࡢࡳ࡬ࡢ㑇ఏᏊᑟධ⬟ࢆ௜ ຍࡋࠊࣜࣥ㓟࢝ࣝࢩ࣒࢘⣔㑇ఏᏊᑟධ๣ࡢḞⅬ࡛࠶ࡿ㑇ఏᏊᑟධຠ⋡ࢆᨵၿ࡛ࡁ ࢀࡤࠊ෌⏕་⒪⏝ᮦᩱ࡜ࡋ࡚኱ኚ᭷ᮃ࡛࠶ࡿ࡜ᮇᚅࡉࢀࡿࠋࡑࡇ࡛ᮏ◊✲࡛ࡣࠊ 㸦㸯㸧 D - C a P ᒙ ୖ ࡟ ࠾ ࡅ ࡿ ሙ ᡤ ≉ ␗ ⓗ 㑇 ఏ Ꮚ ᑟ ධ ἲ ࡢ 㛤 Ⓨ ࠊ㸦㸰㸧 D - C a P ᒙ ࡬ ࡢ ⁐ ゎ ᛶ ไ ᚚ ᅉ Ꮚ ᢸ ᣢ ࡟ ࡼ ࡿ 㑇 ఏ Ꮚ ᑟ ධ ᫬ ᮇ ࡢ ࢥ ࣥ ࢺ ࣟ ࣮ ࣝ ࠊ㸦㸱㸧 D C a P ᒙ ࡬ ࡢ ᢠ య ᢸ ᣢ ࡟ ࡼ ࡿ ≉ ᐃ ⣽ ⬊ ⭘ ࡬ ࡢ 㑇 ఏ Ꮚ ᑟ ධ ຠ ⋡ ࡢ ྥ ୖ ࠊ㸦㸲㸧 D CaP ᒙ࡬ࡢ⬡㉁ᢸᣢ࡟ࡼࡿ㑇ఏᏊᑟධຠ⋡ࡢྥୖࢆ┠ⓗ࡜ࡋࡓࠋ࡞࠾ࠊᮏ◊✲ ࡛ࡣࣜࣥ㓟࢝ࣝࢩ࣒࢘࡜ࡋ࡚≉࡟ࣁ࢖ࢻࣟ࢟ࢩ࢔ࣃࢱ࢖ࢺࢆ⏝࠸ࡓ DNA /࢔ࣃ ࢱ ࢖ ࢺ ࢼ ࣀ 」 ྜ ᒙ 㸦 ௨ ୗ ࠊ D–Ap ᒙ 㸧 ࡢ タィ ࣭ ᵓ ⠏ ࢆ ヨ ࡳ ࡓ ࠋ ᮏ ㄽ ᩥ ࡣ 㸵 ❶ ࡟ ࡼ ࡾ ᵓ ᡂ ࡉ ࢀ ࡚ ࠸ ࡿ ࠋ ➨㸯❶࡛ࡣࠊᮏㄽᩥࡢ◊✲⫼ᬒ࡜┠ⓗࠊࡑࡋ࡚ᴫせ࡟ࡘ࠸࡚㏙࡭࡚࠸ࡿࠋ࢔ࣃࢱ ࢖ࢺࡢᙧᡂ᪉ἲ࡜ࡋ࡚ࡣࠊ↝⤖ἲࠊࣉࣛࢬ࣐⁐ᑕἲࠊࢰࣝ-ࢤࣝἲࠊ࢔ࣝ࢝ࣜỈ ⇕ἲ࡞࡝ࡀᣲࡆࡽࢀࡿࡀࠊᮏㄽᩥ࡛ࡣࣜࣥ㓟࢝ࣝࢩ࣒࢘㐣㣬࿴⁐ᾮࢆ⏝࠸ࡓඹỿ ἲ࡟ࡼࡾ D-Ap ᒙࢆ㧗ศᏊᇶᮦ⾲㠃࡟ᙧᡂࡋࡓࠋDNA ࢆῧຍࡋࡓᖖ ࣭ᖖᅽ ࡢ CaP 㐣㣬࿴⁐ᾮ୰࡟ࡇࢀࡽࡢᇶᮦࢆᾐₕࡍࡿ࡜ࠊCaP ⤖ᬗ࡜ DNA ศᏊࡢ ඹỿ཯ᛂ࡟ࡼࡗ࡚ᇶᮦ⾲㠃࡟ D-Ap ᒙࢆᙧᡂ࡛ࡁࡿࠋࡉࡽ࡟ࠊCaP 㐣㣬࿴⁐ ᾮ୰࡟ DNA ࡜࡜ࡶ࡟ྛ✀ᶵ⬟ศᏊ㸦⁐ゎᛶไᚚᅉᏊࠊ⣽⬊᥋╔ศᏊࠊᢠయࠊ⬡ ㉁࡞࡝㸧ࢆᢸᣢࡋࡓ D-Ap ᒙࢆᙧᡂࡋࡓࠋࡇࡢඹỿᙧᡂࡢࣉࣟࢭࢫ࡟ࡣ CaP ⤖ᬗ࠾ࡼࡧ DNA ศᏊࠊᶵ⬟ศᏊ࡜ࡢ㟼㟁ⓗ┦஫స⏝ࡀ㛵୚ࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀ ࡿࠋᮏ◊✲࡛㛤Ⓨࡋࡓ D-Ap ᒙᙧᡂἲࡢ฼Ⅼ࡜ࡋ࡚ࡣࠊయᾮ࡟㢮ఝࡋࡓ CaP 㐣㣬࿴⁐ᾮࢆ⏝࠸ࡓ࣐࢖ࣝࢻ࡞⎔ቃ࡛ඹỿ཯ᛂࢆ㉳ࡇࡍࡇ࡜࡛ࠊD-Ap ᒙ୰ࡢ DNA ࠾ࡼࡧྛ✀ᶵ⬟ศᏊࡢ⏕⌮άᛶ࣭ᶵ⬟ࢆ࠶ࡿ⛬ᗘಖᣢࡍࡿࡇ࡜ࡀ࡛ࡁࡿ ࡇ࡜ࡀᣲࡆࡽࢀࡿࠋࡲࡓࠊࡇࡢඹỿᙧᡂἲ࡟ࡼࢀࡤ࣐ࢺࣜࢵࢡࢫ࡛࠶ࡿ D-Ap ᒙࡢෆ㒊࡟ࡶ DNA ࠾ࡼࡧᶵ⬟ศᏊࢆᢸᣢ࡛ࡁࡿࡢ࡛ࠊ࠶ࡽ࠿ࡌࡵ㧗ศᏊᇶᮦ⾲㠃࡟ᙧᡂࡋࡓ࢔ࣃࢱ࢖ࢺᒙࡢ⾲㠃࡟ DNA ࠾ࡼࡧྛ✀ᶵ⬟ศᏊࢆ྾╔ࡉࡏࡿ⾲㠃 ྾╔ἲ࡟ẚ࡭࡚ࠊከ㔞ࡢ DNA ࠾ࡼࡧᶵ⬟ศᏊࢆᢸᣢࡋࠊᚎᨺ⬟ࢆ௜୚࡛ࡁࡿࠋ ➨ 㸰 ❶ ࡛ ࡣ ࠊࠕ D N A 㸫 ࣇ ࢕ ࣈ ࣟ ࢿ ࢡ ࢳ ࣥ 㸫 ࢔ ࣃ ࢱ ࢖ ࢺ 」 ྜ ᒙ 㸦 ௨ ୗ ࠊ D F - A p ᒙ㸧ୖ࡟࠾ࡅࡿሙᡤ≉␗ⓗ㑇ఏᏊᑟධࠊཬࡧศ໬ㄏᑟࠖ࡟ࡘ࠸࡚㏙࡭࡚࠸ࡿࠋ ࡞࠾ࣇ࢕ࣈࣟࢿࢡࢳࣥࡣ⣽⬊᥋╔ᛶࢱࣥࣃࢡ㉁ࡢ୍✀࡛ࠊ⣽⬊⾲㠃࡟Ꮡᅾࡍࡿࣞ ࢭࣉࢱ࣮࡜⤖ྜࡍࡿᛶ㉁ࢆ᭷ࡍࡿࠋࡇࡢࣇ࢕ࣈࣟࢿࢡࢳࣥࢆ D-Ap ᒙ࡟ᢸᣢࡍ ࡿࡇ࡜࡛ྠᒙ⾲㠃࡟࠾ࡅࡿ⣽⬊᥋╔ࢆಁ㐍ࡋࠊ㑇ఏᏊᑟධຠ⋡ࢆྥୖࡉࡏࡿຠᯝ ࡀ࠶ࡿࠋᮏ❶࡛ࡣࠊ␗࡞ࡿ㑇ఏᏊࢆᢸᣢࡉࡏࡓ 2 ✀㢮ࡢ DF-Ap 」ྜᒙࢆ 1 ࡘ ࡢ࢙࢘ࣝෆ࡛㞄᥋ࡉࡏࠊࡑࡢ⾲㠃࡛⣽⬊ࢆᇵ㣴ࡍࡿࡇ࡜࡟ࡼࡾࠊࡑࢀࡒࢀࡢ」ྜ ᒙ⾲㠃࡟᥋╔ࡋࡓ⣽⬊࡟ࠊࡑࡢ」ྜᒙ࡟ᢸᣢࡉࡏࡓ㑇ఏᏊࡢࡳࢆሙᡤ≉␗ⓗ࡟ᑟ ධࡍࡿᡭἲࢆ☜❧ࡋࡓࠋࡲࡓࠊࡑࢀ࡟ࡼࡗ࡚㞄᥋ࡋࡓྛᇶᯈ⾲㠃࡟᥋╔ࡋࡓ⣽⬊ ࢆࡑࢀࡒࢀูࡢ᪉ྥ࡟ศ໬ㄏᑟ࡛ࡁࡿྍ⬟ᛶࢆ♧ࡋࡓࠋᮏ◊✲࡛☜❧ࡋࡓ DFAp 」ྜᒙࢆ⏝࠸ࡓ㑇ఏᏊᑟධἲ࡟ࡼࡾࠊ┠ⓗࡢ㑇ఏᏊࢆ┠ⓗࡢሙᡤࡢ⣽⬊࡟㑅 ᢥ ⓗ ࡟ ᑟ ධ ࡋ ࠊ ࡑ ࡢ ศ ໬ ࢆ ㄏ ᑟ ࡛ ࡁ ࡿ ࡇ ࡜ ࡀ ᫂ ࡽ ࠿ ࡟ ࡞ ࡗ ࡓ ࠋ ➨ 㸱 ❶ ࡛ ࡣ ࠊࠕ Ⅳ 㓟 ࢖ ࢜ ࣥ ࠊ ཬ ࡧ ࣇ ࢵ ໬ ≀ ࢖ ࢜ ࣥ ࡢ ࢻ ࣮ ࣉ ࡟ ࡼ ࡿ D F - A p ᒙ ୖ ࡟࠾ࡅࡿ㑇ఏᏊᑟධຠ⋡ࠊཬࡧᑟධ᫬ᮇࡢไᚚࠖ࡟ࡘ࠸࡚㏙࡭࡚࠸ࡿࠋᮏ❶࡛ࡣ ࡲࡎࠊࢥ࣮ࢸ࢕ࣥࢢ⁐ᾮ୰࡜ࡋ࡚⏝࠸ࡽࢀࡿ CaP 㐣㣬࿴⁐ᾮ୰࡬ NaHCO 3 ࠊ࠶ࡿ࠸ࡣ NaF ࢆῧຍࡍࡿࡇ࡜࡛ࠊᙧᡂࡉࢀࡿ DF-Ap ᒙ࡟Ⅳ㓟࢖࢜ࣥࠊ࠶ ࡿ࠸ࡣࣇࢵ໬≀࢖࢜ࣥࢆࢻ࣮ࣉࡉࡏࡿᢏ⾡ࢆ☜❧ࡋࡓࠋⅣ㓟࢖࢜ࣥࡢࢻ࣮ࣉ࡟ࡼ ࡾ DF-Ap ᒙࡢ⁐ゎᛶࢆྥୖࡉࡏࠊ୍᪉ࣇࢵ໬≀࢖࢜ࣥࡢࢻ࣮ࣉ࡟ࡼࡾ DFAp ᒙࡢ⁐ゎᛶࢆపୗࡉࡏࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡑࡋ࡚ᚓࡽࢀࡓྛ DF-Ap ᒙ⾲㠃 ࡛ᇵ㣴ࡋࡓ⣽⬊࡬ࡢ㑇ఏᏊᑟධຠ⋡ࡀࠊྠ」ྜᒙࡢ⁐ゎᛶ࡜ṇࡢ┦㛵ࢆ♧ࡍࡇ࡜ ࢆぢฟࡋࡓࠋࡍ࡞ࢃࡕࠊDF-Ap ᒙࡢ⁐ゎᛶࢆไᚚࡍࡿࡇ࡜࡛ࡑࡢ⾲㠃࡟࠾ࡅ ࡿ㑇ఏᏊᑟධຠ⋡ࢆไᚚ࡛ࡁࡿࡇ࡜ࢆぢฟࡋࡓࠋࡲࡓࠊDF-Ap ᒙࡢ⁐ゎᛶࢆ పୗࡉࡏࡿࡇ࡜࡛ࠊྠ」ྜᒙ⾲㠃ୖ࡛㑇ఏᏊᑟධࡀ㉳ࡇࡿ᫬ᮇࢆ㐜ᘏࡉࡏࡿࡇ࡜ ࡀ࡛ࡁࡓࠋ௨ୖࡼࡾࠊࢥ࣮ࢸ࢕ࣥࢢ⁐ᾮ୰࡬ࡢ NaF ࡸ NaHCO 3 ࡢῧຍ࡟ࡼ ࡾࠊྠᾮ୰࡛ᙧᡂࡉࢀࡿ DF-Ap ᒙࡢ⁐ゎᛶࢆไᚚ࡛ࡁࠊࡑࢀ࡟ࡼࡾྠ」ྜᒙ ⾲㠃࡟࠾ࡅࡿ㑇ఏᏊᑟධࡢຠ⋡ࡸ᫬ᮇࢆไᚚ࡛ࡁࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋ ➨ 㸲 ❶ ࡛ ࡣ ࠊࠕ D N A 㸫 ᢠ య 㸫 ࢔ ࣃ ࢱ ࢖ ࢺ 」 ྜ ᒙ 㸦 ௨ ୗ ࠊ D A - A p ᒙ 㸧 ୖ ࡟ ࠾ ࡅࡿ⣽⬊≉␗ⓗ㑇ఏᏊᑟධࠖ࡟ࡘ࠸࡚㏙࡭࡚࠸ࡿࠋ࡞࠾ࠊᢠయࡣࣇ࢕ࣈࣟࢿࢡࢳ ࣥ࡜␗࡞ࡾ㠀ᖖ࡟㧗࠸≉␗ᛶࢆᣢࡗ࡚ᢠཎ࡟᥋╔ࡍࡿࢱࣥࣃࢡ㉁࡛࠶ࡿࠋᢠయࡣ ┠ⓗࡢ⣽⬊ࡢ⾲㠃࡟Ꮡᅾࡍࡿࢱࣥࣃࢡ㉁ࢆᢠཎ࡜ࡍࡿࡶࡢࢆ⏝࠸ࡓࠋᮏ❶࡛ࡣࡲ ࡎࠊᢠయࡢᢠయ-ᢠཎ཯ᛂάᛶࢆኻάࡉࡏࡿࡇ࡜࡞ࡃࠊDA-Ap ᒙࢆᙧᡂࡉࡏ ࡿᢏ⾡ࢆ☜❧ࡋࡓࠋࡑࡋ࡚ᚓࡽࢀࡓ DA-Ap ᒙ⾲㠃࡛ᇵ㣴ࡋࡓ⣽⬊ࡢ࠺ࡕࠊ┠ ⓗࡢ⣽⬊࡬ࡢࡳࠊ㑇ఏᏊᑟධຠ⋡ࢆྥୖࡉࡏࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡍ࡞ࢃࡕࠊᢠయᢠཎ཯ᛂ࡟㧗࠸≉␗ᛶࢆ฼⏝ࡋࡓ⣽⬊≉␗ⓗ࡞㑇ఏᏊᑟධࡢྍ⬟ᛶࢆぢฟࡋࡓࠋ ➨ 㸳 ❶ ࡛ ࡣ ࠊࠕ D N A 㸫 ⬡ ㉁㸫 ࢔ ࣃ ࢱ ࢖ ࢺ 」 ྜ ᒙ 㸦 ௨ ୗ ࠊ D L - A p ᒙ 㸧 ࢆ ⏝ ࠸ ࡓ㧗ຠ⋡ࠊ࠿ࡘሙᡤ≉␗ⓗ㑇ఏᏊᑟධࠖ࡟ࡘ࠸࡚㏙࡭࡚࠸ࡿࠋ࡞࠾ࠊᮏ❶࡛⏝࠸ ࡓ⬡㉁ࡣࠊࡑࡢศᏊ୰࡟ぶỈ㒊࡜ぶἜ㒊ࢆᣢࡘ୧ぶ፹ᛶ≀㉁ࡢ 1 ✀࡛࠶ࡾࠊỈ⁐ ᾮ୰࡛จ㞟ࡋ࡚ࢼࣀ࠿ࡽࢧࣈ࣑ࢡࣟࣥࢧ࢖ࢬࡢ⢏Ꮚࠕ࣏ࣜࢯ࣮࣒ࠖࢆᙧᡂࡍࡿࠋ ࣏ࣜࢯ࣮࣒ࡢෆ㒊ࡸ⾲㠃࡟ࡣ DNA ࡀ⤖ྜࡋࠊDNA㸫࣏ࣜࢯ࣮࣒ࢥࣥࣉࣞࢵࢡ ࢫࢆᙧᡂࡍࡿࠋࡇࡢ DNA㸫࣏ࣜࢯ࣮࣒ࢥࣥࣉࣞࢵࢡࢫࡀຠ⋡ⓗ࡟⣽⬊ෆ࡟ྲྀࡾ ㎸ࡲࢀࡿࡇ࡜࡛⣽⬊ෆ࡟㑇ఏᏊࡀᑟධࡉࢀࡿࠋ࣏ࣜࢯ࣮࣒ࢆ⏝࠸ࡓᡭἲࡣ㠀࢘࢖ ࣝࢫ⣔࡜ࡋ࡚ࡣࢺࢵࣉࢡࣛࢫࡢ㑇ఏᏊᑟධຠ⋡ࢆ♧ࡍࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋᮏ❶ ࡛ࡣࡲࡎࠊ⬡㉁ࡢ㑇ఏᏊᑟධᶵ⬟ࢆኻࢃࡏࡿࡇ࡜࡞ࡃࠊDL-Ap ᒙࢆᙧᡂࡉࡏ ࡿᢏ⾡ࢆ☜❧ࡋࡓࠋDL-Ap ᒙ࡬ࡢ⬡㉁ࡢᢸᣢ࡟ࡼࡾ㑇ఏᏊᑟධຠ⋡ࢆྥୖࡉ ࡏࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡑࡢ⤖ᯝࠊDL-Ap ᒙ࡟ࡼࡿᑟධຠ⋡ࡣࠊDF-Ap ᒙ࡟ ࡼࡿࡑࢀ࡜ẚ㍑ࡋ࡚ࡶ᭷ព࡟㧗࠸ᑟධຠ⋡ྥୖࢆ㐩ᡂࡋࡓࠋࡲࡓࠊDL-Ap ᒙ ࢆ ⏝ ࠸ ࡚ ሙ ᡤ ≉ ␗ ⓗ ࡟ 㑇 ఏ Ꮚ ࢆ ᑟ ධ ࡛ ࡁ ࡿ ࡇ ࡜ ࡶ ᫂ ࡽ ࠿ ࡟ ࡞ ࡗ ࡓ ࠋ ➨ 㸴 ❶ ࡛ ࡣ ࠊࠕ ඹ ỿ ἲ ࠊ ཬ ࡧ ྾ ╔ ἲ ࡟ ࡼ ࡾ స 〇 ࡋ ࡓ D L - A p ᒙ ࡢ ࠊ 㑇 ఏ Ꮚ ᑟ ධ ࡬ࡢᛂ⏝࡟࠾ࡅࡿẚ㍑ࠖ࡟ࡘ࠸࡚㏙࡭࡚࠸ࡿࠋᮏ❶࡛ࡣࡲࡎࠊඹỿἲ࡜྾╔ἲࡢ ࠸ࡎࢀࡢ᪉ἲ࡛ࡶ⬡㉁ࡢ㑇ఏᏊᑟධᶵ⬟ࢆኻࢃࡏࡿࡇ࡜࡞ࡃࠊDL-Ap ᒙࢆᙧ ᡂࡉࡏࡿᢏ⾡ࢆ☜❧ࡋࡓࠋඹỿἲ࡟ࡼࡾ DNA ࡜⬡㉁ࢆ DL-Ap ᒙෆ㒊࡟ࡲ࡛ ᢸᣢࡉࡏࡿࡇ࡜࡛ࠊ྾╔ἲ࡟ࡼࡾస〇ࡋࡓྠᒙࡼࡾࡶᢸᣢ㔞ࢆቑຍࡉࡏࠊࡼࡾ㛗 ᮇ࡟Ώࡗ࡚ࡑࢀࡽࢆᚎᨺࡉࡏࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡑࡢ⤖ᯝࠊඹỿἲ࡟ࡼࡾస〇ࡋࡓ DL-Ap ᒙ࡟ࡼࡿᑟධຠ⋡ࡣࠊ྾╔ἲ࡟ࡼࡾస〇ࡋࡓྠᒙ࡟ࡼࡿࡑࢀ࡜ẚ㍑ࡋ ࡚ ᭷ ព ࡟ 㧗 ࠿ ࡗ ࡓ ࠋ ➨ 㸵 ❶ ࡛ ࡣ ࠊࠕ 㑇 ఏ Ꮚ ᑟ ධ ࡬ ࡢ ᛂ ⏝ ࡟ ࠾ ࡅ ࡿ D L - A p ᒙ ᙧ ᡂ ᮲ ௳ 㸦 D N A ῧ ຍ ⃰ᗘࠊDNA㸭⬡㉁ẚ⋡㸧ࡢ᭱㐺໬ࠖ࡟ࡘ࠸࡚㏙࡭࡚࠸ࡿࠋᮏ❶࡛ࡣࡲࡎࠊ✀ࠎ ࡢ DNA ῧຍ⃰ᗘࠊDNA㸭⬡㉁ẚ⋡ࡢ DL-Ap ᒙࢆᙧᡂࡉࡏࡿᢏ⾡ࢆ☜❧ࡋ ࡓࠋࡑࢀࡒࢀ 2 ✀㢮ࡢ⬡㉁ࢆ⏝࠸࡚ DL-Ap ᒙࢆᙧᡂࡉࡏࡓ⤖ᯝࠊ⬡㉁ࡈ࡜࡟ 」ྜᒙᙧᡂ᮲௳ࢆࡑࢀࡒࢀ᭱㐺໬ࡍࡿᚲせࡀ࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋ ➨㸶❶ࡣࠕ⤖ㄽ࡛ࠖ࠶ࡿࠋᮏ❶࡛ࡣࠊᮏㄽᩥࡢᡂᯝࢆ⥲ᣓࡋࠊࡉࡽ࡟෌⏕་⒪ࡸ 㑇 ఏ Ꮚ ἞ ⒪ ࡞ ࡝ ࡬ ࡢ ᛂ ⏝ ᒎ 㛤 ࡢ ྍ ⬟ ᛶ ࡟ ࡘ ࠸ ࡚ ㏙ ࡭ ࡚ ࠸ ࡿ ࠋ 㹌㹭 ᪩✄⏣኱Ꮫ ༤ኈ㸦ᕤᏛ㸧 Ꮫ఩⏦ㄳ ◊✲ᴗ⦼᭩ Ặྡ ▮ᓮౡ᣺ ༳ 㸦㸰㸮㸯㸱ᖺ 㸳᭶ ⌧ᅾ㸧 ✀㢮ู 㢟ྡࠊ Ⓨ⾲࣭Ⓨ⾜ᥖ㍕ㄅྡࠊ Ⓨ⾲࣭Ⓨ⾜ᖺ᭶ࠊ 㐃ྡ⪅㸦⏦ㄳ⪅ྵࡴ㸧 ➹㢌ㄽᩥ ‫ ۑ‬Coprecipitation of DNA-lipid complexes with apatite and comparison with superficial 㸦ᰝㄞ᭷㸧 adsorption for gene transfer applications Yushin Yazaki, Ayako Oyane, Hideo Tsurushima, Hiroko Araki, Yu Sogo, Atsuo Ito, and Atsushi Yamazaki Journal of Biomaterials Applications.㸦ᥖ㍕Ỵᐃ㸧 ‫ ۑ‬Fabrication of DNA-antibody-apatite composite layers for cell-targeted gene transfer Yushin Yazaki, Ayako Oyane, Hiroko Araki, Yu Sogo, Atsuo Ito, Atsushi Yamazaki, Hideo Tsurushima Science and Technology of Advanced Materials. 2012, 13, 064204 ‫ ۑ‬Control of gene transfer on a DNA-fibronectin-apatite composite layer by the incorporation of carbonate and fluoride ions Yushin Yazaki, Ayako Oyane, Yu Sogo, Atsuo Ito, Atsushi Yamazaki, Hideo Tsurushima Biomaterials. 2011, 32, 4896 ‫ ۑ‬Control of Efficiency of Gene Transfer on Surface of DNA–Fibronectin–Apatite Composite Layer YushinYazaki, Ayako Oyane, Hideo Tsurushima, Yu Sogo, Atsuo Ito, Atsushi Yamazaki Bioceramics. 2009, 22, 547 ඹⴭㄽᩥ ‫ ۑ‬Fabrication of a DNA-lipid-apatite composite layer for efficient and area-specific gene 㸦ᰝㄞ᭷㸧 transfer Ayako Oyane, Yushin Yazaki, Hiroko Araki, Yu Sogo, Atsuo Ito, Atsushi Yamazaki, Hideo Tsurushima Journal of Materials Science: Materials in Medicine. 2012, 23, 1011 BMP-2 gene-fibronectin-apatite composite layer enhances bone formation Wei Zhang, Hideo Tsurushima, Ayako Oyane, Yushin Yazaki, Yu Sogo, Atsuo Ito, Akira Matsumura Journal of Biomedical Science. 2011, 18, 62 Inhibition of hydrogen embrittlement of Ni-Ti superelastic alloy in acid fluoride solution by hydrogen peroxide addition Ken’ich Yokoyama, Yushin Yazaki, Jun’ich Sakai Journal of Biomedical Materials Research Part A. 2011, 98, 404 Hydrogen Absorption and Thermal Desorption Behavior of Ni-Ti Superelastic Alloy Immersed in Neutral NaCl and NaF Solutions under Applied Potential Asahi Ota, Yushin Yazaki, Ken’ich Yokoyama, Jun’ich Sakai Materials Transactions. 2009, 50, 1843 ඹⴭ⥲ㄝ ‫ ۑ‬Gene transfer system using calcium phosphate composite layers for tissue engineering 㸦ᰝㄞ᭷㸧 applications Ayako Oyane, Yushin Yazaki, Hideo Tsurushima, Xiupeng Wang, Yu Sogo, Atsuo Ito, Atsushi Yamazaki Journal of the Society of Inorganic Materials,Japan. 2012, 19, 466 㹌㹭 ᪩✄⏣኱Ꮫ ༤ኈ㸦ᕤᏛ㸧 Ꮫ఩⏦ㄳ ◊✲ᴗ⦼᭩ ✀㢮ู 㢟ྡࠊ Ⓨ⾲࣭Ⓨ⾜ᥖ㍕ㄅྡࠊ Ⓨ⾲࣭Ⓨ⾜ᖺ᭶ࠊ 㐃ྡ⪅㸦⏦ㄳ⪅ྵࡴ㸧 ㅮ₇ 㸦➹㢌㸧 ‫ ۑ‬Effect of ion incorporation into a DNA-fibronectin-apatite composite layer on its gene transfer capability Yushin Yazaki, Ayako Oyane, Atsuo Ito, Yu Sogo, Hiroko Araki, Atsushi Yamazaki, Hideo Tsurushima 2012 ᖺ 6 ᭶ The 9th World Biomaterials Congress ‫ ۑ‬ᢠయᢸᣢ࡟ࡼࡿ DNA-࢔ࣃࢱ࢖ࢺ」ྜᒙࡢ㑇ఏᏊᑟධ⬟ྥୖ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ㭯ᔱⱥኵࠊⲨᮌ⿱Ꮚࠊ༑Ἑ཭ࠊఀ⸨ᩔኵࠊᒣ㷂ᩔྖ 2012 ᖺ 1 ᭶ ࡘࡃࡤ་ᕤ㐃ᦠࣇ࢛࣮࣒ࣛ 2012 ‫ ۑ‬Antibody immobilized in a DNA-apatite composite layer enhances gene transfer efficiency Yushin Yazaki, Ayako Oyane, Hideo Tsurushima, Yu Sogo, Atsuo Ito, Atsushi Yamazaki 2011 ᖺ 11 ᭶ 11th Asian BioCeramics Symposium ‫࣒࣮ࢯ࣏ࣜ ۑ‬í࢔ࣃࢱ࢖ࢺ」ྜᒙࢆ฼⏝ࡋࡓ㑇ఏᏊᑟධࢩࢫࢸ࣒ ʊ࣏ࣜࢯ࣮࣒ᵓᡂ ศᏊࡢ᳨ウʊ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ༑Ἑ཭ࠊఀ⸨ᩔኵࠊᒣᓮ῟ྖࠊ㭯ᔱⱥኵ 2010 ᖺ 3 ᭶ ᪥ᮏࢭ࣑ࣛࢵࢡࢫ༠఍ 2010 ᖺᖺ఍ ‫࣒࣮ࢯ࣏ࣜ ۑ‬-࢔ࣃࢱ࢖ࢺ」ྜᒙࢆ฼⏝ࡋࡓ㑇ఏᏊᑟධᢏ⾡ࡢ㛤Ⓨ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ㭯ᔱⱥኵࠊ༑Ἑ཭ࠊఀ⸨ᩔኵࠊᒣ㷂῟ྖ 2010 ᖺ 1 ᭶ ᪥ᮏࢭ࣑ࣛࢵࢡࢫ༠఍➨ 48 ᅇࢭ࣑ࣛࢵࢡࢫᇶ♏⛉Ꮫウㄽ఍ ‫ ۑ‬DNA–ᢠయ–࢔ࣃࢱ࢖ࢺ」ྜᒙࢆ฼⏝ࡋࡓ 㑇ఏᏊᑟධᢏ⾡ࡢ㛤Ⓨ ▮ᓮౡ᣺ࠊ㭯ᔱⱥኵࠊ኱▮᰿⥤Ꮚࠊ༑Ἑ཭ࠊᒣᓮ῟ྖࠊఀ⸨ᩔኵ 2009 ᖺ 11 ᭶ ➨ 31 ᅇ᪥ᮏࣂ࢖࣐࢜ࢸࣜ࢔ࣝᏛ఍኱఍ ‫ ۑ‬Control of Efficiency of Gene Transfer on Surface of DNA–Fibronectin–Apatite Composite Layer Yushin Yazaki, Ayako Oyane, Hideo Tsurushima, Yu Sogo, Atsuo Ito, Atsushi Yamazaki 2009 ᖺ 10 ᭶ The 22nd International Symposium on Ceramics in Medicine ‫⾲ࢺ࢖ࢱࣃ࢔ ۑ‬㠃࡟࠾ࡅࡿ⣽⬊࡬ࡢ㑇ఏᏊᑟධຠ⋡ࡢไᚚ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ㭯ᔱⱥኵࠊ༑Ἑ཭ࠊఀ⸨ᩔኵࠊᒣᓮ῟ྖ 2009 ᖺ 3 ᭶ ᪥ᮏࢭ࣑ࣛࢵࢡࢫ༠఍ 2009 ᖺᖺ఍ ‫⾲ࢺ࢖ࢱࣃ࢔ ۑ‬㠃࡟࠾ࡅࡿ㑇ఏᏊᑟධࡢ᫬㛫ⓗࢥࣥࢺ࣮ࣟࣝ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ㭯ᔱⱥኵࠊᒣ㷂῟ྖࠊ༑Ἑ཭ࠊఀ⸨ᩔኵ 2009 ᖺ 1 ᭶ ࡘࡃࡤ་ᕤ㐃ᦠࣇ࢛࣮࣒ࣛ 2009 ‫⾲ࢺ࢖ࢱࣃ࢔ ۑ‬㠃࡟࠾ࡅࡿ㑇ఏᏊᑟධࡢ✵㛫ⓗ࣭᫬㛫ⓗࢥࣥࢺ࣮ࣟࣝ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ㭯ᔱⱥኵࠊᒣ㷂῟ྖࠊ༑Ἑ཭ࠊఀ⸨ᩔኵ 2009 ᖺ 1 ᭶ ᪥ᮏࢭ࣑ࣛࢵࢡࢫ༠఍➨ 47 ᅇࢭ࣑ࣛࢵࢡࢫᇶ♏⛉Ꮫウㄽ఍ 㹌㹭 ᪩✄⏣኱Ꮫ ༤ኈ㸦ᕤᏛ㸧 Ꮫ఩⏦ㄳ ◊✲ᴗ⦼᭩ ✀㢮ู 㢟ྡࠊ Ⓨ⾲࣭Ⓨ⾜ᥖ㍕ㄅྡࠊ Ⓨ⾲࣭Ⓨ⾜ᖺ᭶ࠊ 㐃ྡ⪅㸦⏦ㄳ⪅ྵࡴ㸧 ‫ ۑ‬⣽⬊᥋╔ᛶࢱࣥࣃࢡ㉁-࢔ࣃࢱ࢖ࢺ」ྜᒙࢆ⏝࠸ࡓ㑇ఏᏊᑟධἲࡢ㛤Ⓨ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ㭯ᔱⱥኵࠊᮧᒣ㞞⨾ࠊᒣᓮ῟ྖࠊ༑Ἑ཭ࠊఀ⸨ᩔኵ 2008 ᖺ 12 ᭶ ᪥ᮏࢭ࣑ࣛࢵࢡࢫ༠఍➨ 12 ᅇ⏕య㛵㐃ࢭ࣑ࣛࢵࢡࢫウㄽ఍ 㐣㓟໬Ỉ⣲ῧຍ࡟ࡼࡿࣇࢵ໬≀Ỉ⁐ᾮ୰࡟࠾ࡅࡿ Ni-Ti ㉸ᙎᛶྜ㔠ࡢỈ⣲⬤໬ᢚไ ▮ᓮౡ᣺ࠊᶓᒣ㈼୍ࠊ㓇஭₶୍ 2008 ᖺ 3 ᭶ ᪥ᮏ㔠ᒓᏛ఍➨ 143 ᅇ᫓Ꮨ኱఍ ㅮ₇ 㸦ඹⴭ㸧 ‫ ۑ‬Biomimetic calcium phosphate coating and application to gene delivery Ayako Oyane, Yushin Yazaki, Wei Zhang, Xiupeng Wang, Yu Sogo, Atsuo Ito, Atsushi Yamazaki, Hideo Tsurushima 2013 ᖺ 6 ᭶ The 4th Asian Biomaterials Congress ‫ ۑ‬㑇ఏᏊᑟධᶵ⬟ࢆ᭷ࡍࡿ࢔ࣃࢱ࢖ࢺ」ྜᒙࡢタィ࡜ᛂ⏝ ኱▮᰿⥤Ꮚࠊ▮ᓮౡ᣺ࠊ⋤⚽㭉ࠊ༑Ἑ཭ࠊఀ⸨ᩔኵࠊᒣᓮ῟ྖࠊ㭯ᔱⱥኵ 2012 ᖺ 11 ᭶ ᪥ᮏࣂ࢖࣐࢜ࢸࣜ࢔ࣝᏛ఍ࢩ࣏ࣥࢪ࣒࢘ 2012 ‫ ۑ‬A DNA–lipid–apatite composite layer mediates efficient and area-specific gene transfer Ayako Oyane, Yushin Yazaki, Hiroko Araki, Yu Sogo, Atsuo Ito, Atsushi Yamazaki, Hideo Tsurushima 2012 ᖺ 6 ᭶ The 9th World Biomaterials Congress ‫ ۑ‬Area-specific gene transfer on a DNA௅fibronectin௅apatite composite layer Ayako Oyane, Yushin Yazaki, Hideo Tsurushima, Yu Sogo, Atsuo Ito, Atsushi Yamazaki 2011 ᖺ 11 ᭶ 11th Asian BioCeramics Symposium ‫ ۑ‬Control of efficiency and timing of gene transfer on apatite-based composite layer Ayako Oyane, Hideo Tsurushima, Yushin Yazaki, Hiroko Araki, Yu Sogo, Atsuo Ito, Atsushi Yamazaki 2011 ᖺ 3 ᭶ International Conference on Biomaterials Science 2011 ‫ྜ」ࢺ࢖ࢱࣃ࢔ ۑ‬ᒙࢆ฼⏝ࡋࡓሙᡤ≉␗ⓗ㑇ఏᏊᑟධ ኱▮᰿⥤Ꮚ㸪▮ᓮౡ᣺㸪㭯ᔱⱥኵ㸪༑Ἑ཭㸪ఀ⸨ᩔኵ㸪ᒣ㷂῟ྖ 2011 ᖺ 1 ᭶ ࡘࡃࡤ་ᕤ㐃ᦠࣇ࢛࣮࣒ࣛ 2011 ࡑࡢ௚ 3 ௳ ࡑࡢ௚ 㸦ཷ㈹㸧 ‫ ۑ‬ABC award Yushin Yazaki, Ayako Oyane, Hideo Tsurushima, Yu Sogo, Atsuo Ito, Atsushi Yamazaki 2011 ᖺ 11 ᭶ 11th Asian BioCeramics Symposium ‫ ۑ‬᭱ඃ⚽Ⓨ⾲㈹ ▮ᓮౡ᣺ࠊ኱▮᰿⥤Ꮚࠊ㭯ᔱⱥኵࠊᮧᒣ㞞⨾ࠊᒣᓮ῟ྖࠊ༑Ἑ཭ࠊఀ⸨ᩔኵ 2008 ᖺ 12 ᭶ ᪥ᮏࢭ࣑ࣛࢵࢡࢫ༠఍➨ 12 ᅇ⏕య㛵㐃ࢭ࣑ࣛࢵࢡࢫウㄽ఍ ࡑࡢ௚ 㸦≉チ㸧 9 ௳ฟ㢪