Since 1874 遺伝子治療とゲノム編集治療の 研究開 …

1 NIHSS ince 1874 NIHSS ince 1874 1 1 2 3 Invivo ex vivo ( ) T AAV DNA 7 4*J Gene data B ADA LPL HIV/AIDS B ALS 65% 11% 7% 7% 2% 1% 7%5 1970 DNA

2 1990 ADA 1995 ADA 1999 2000 X-SCID 2002 X-SCID 2008 2012 ASGCT Target 10 5-7 2012 AAV) 2015 HSV) 2016 2 ADA GVHD 2017 CAR-T 2 1 6 6 Glybera UniQure AAV1 S447X LPL 2012 2017 Imlygic Amgen HSV1GM-CSF 2015 Strimvelis GSK - ADAADA 2016 Zalmoxis MolMed -T HSV-TK Mut2 / LNGFR GVHD 2016 Kymriah(Novartis) -T CAR-T ) CD19 B 2017 Yescarta(Kite Pharma) -T CAR-T ) CD19 B 2017 Luxturna Spark Therapeutics)

3 AAV2 RPE65 2017 7 January 6, 2012 From: the American Society of Gene & Cell Therapy and all the Society s past PresidentsTo: NIH Director, Francis S Collins Target 10 group of disease and disorders 1. Spark 2017 GSK 2016 3. B Baxter SparkPhase Phase I/II 5. Phase I)6. Sanofi-Genzyme (Phase I)7. Bluebird Bio (Phase II/III)8. ( Bluebird Bio (Phase II/III)9. Novartis, Kite Pharma 2017 10. Amgen 20152012 Target 10 4 2017 Target 10 8 ex vivo ex vivo in vivo (AAV)

4 In vivo < in vivo 99 ex vivo in vivo A AV 1 T CAR-T 10 80% 2017 2 T CAR(Chimeric Antigen Receptor) T CAR-T CAR-T CAR -T CAR T 11 in vivo shedding)

5 1 12 13 2597 * *1 USA16432UK2213 Multi-Country1304 Germany925 China846 France597 Switzerland508 Japan44*(66**)9 Netherlands3410 Australia32*J Gene ** ** GlyberaEU T-vec X-SCID 66 ** 0123456789109596979899000102030405060708 09101112131415161718 15** 32% 25% 22%HSV110% 6%AAV5% 71% 15% 14%16 60 1 AAV AAV

6 IND 17 18 (Genome editing) ( ( DNA ( ) KO) DNA 19 20 : ZFN 1996 (Zinc Finger Nuclease) 2 : TA L E N2010 (Transcription Activator Like Effector Nuclease) 2.)

7 CRISPR/Cas2012 (Clustered Regularly Interspaced Short Palindromic Repeats / CRISPR associated protein) RNA RNA 21 Mol. Ther. 24, 430 2016 HSC, T cell, iPScell in vivo ex vivo T iPS 22 Mol. , 430 2016 Duchenne Cystic fibrosis : PCSK9 HBV X SCID, ADA SCID, RS SCID, Sickle cell disease, T HIV 23 )

8 CRISPR/Cas9 TA LE N 0123456789102009201020112012201320142015 20162017 CRISPRTALENZFN 24 CAR T 11 CAR-T T CAR-T CAR-T CAR T KOX KO X25 B 9 / 26 AAV2/6 1 ZFN1, ZFN2 2017 Sangamo 26 AAV mRNA ( DDS 27 28)

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