参考文献

01 基因的秘密

Avery, O. T.，MacLeod, C.M.，and McCarty, M.（1944）.Studies on the chemical nature of the substance inducing transformation of pneumococcal types：induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III.J Exp Med 79，137-158.

Cobb, M.（2006）. Heredity before genetics：a history.Nat Rev Genet 7，953-958.

Cobb, M.（2014）. Oswald Avery, DNA, and the transformation of biology.Curr Biol 24，R55-R60.

Cobb, M.（2016）. A Speculative History of DNA：What If Oswald Avery Had Died in 1934?PLoS Biol 14，e2001197.

Davenport, C. B.（1937）.Home of the Ancon Sheep.Science 86，422-422.

Diamond, J.（1997）. Guns, Germs, and Steel：The Fates of Human Societies（W.W.Norton）.

Eichmann, K.，and Krause, R. M.（2013）.Fred Neufeld and pneumococcal serotypes：foundations for the discovery of the transforming principle.Cell Mol Life Sci 70，2225-2236.

Franklin, R. E.，and Gosling, R.G.（1953）.Molecular configuration in sodium thymonucleate.Nature 171，740-741.

Griffth, F.（1928）. The Signifcance of Pneumococcal Types.J Hyg（Lond）27，113-159.

Harari, Y.（2014）. Sapiens：A Brief History of Humankind（Harper）.

Hartl, D.，and Jones, E.（2005）. Genetics：Analysis of Genes and Genomes（Jones&Barlett）.

Hershey, A. D.，and Chase, M.（1952）.Independent functions of viral protein and nucleic acid in growth of baceriophage.J Gen Physiol 36，39-56.

Judson, H. F.（1996）.The Eighth Day of Creation：Makers of the Revolution in Biology（Touchstone Books）.

Leder, P.（2010）. Marshall Warren Nirenberg（1927-2010）.Science 327，972-972.

Leder, P.，and Nirenberg, M. W.（1964）.RNA codewords and protein synthesis, III.The nucleotide sequence of a cysteine and a leucine RNA codeword.Proc Natl Acad Sci USA 52，1521-1529.

Lorenz, M. G.，and Wackernagel, W.（1994）.Bacterial gene transfer by natural genetic transformation in the environment.Microbiol Rev 58，563-602.

McCarty, M.（2003）. Discovering genes are made of DNA.Nature 421，406-406.

Meselson, M.，and Stahl, F. W.（1958）.The replication of DNA in Escherichia coli.Proc Natl Acad Sci USA 44，671-682.

Watson, J. D.，and Crick, F.H.（1953）.Molecular structure of nucleic acids；a structure for deoxyribose nucleic acid.Nature 171，737-738.

Wilkins, M. H.，Stokes, A.R.，and Wilson, H.R.（1953）.Molecular structure of deoxypentose nucleic acids.Nature 171，738-740.

Witting, L.（2008）. Inevitable evolution：back to the origin and beyond the 20th century paradigm of contingent evolution by historical natural selection.Biol Rev Camb Philos Soc 83，259-294.

02 给基因动手术

Anderson, W. F.（1990）.September 14，1990：The Beginning.Hum Gene Ther 1，371-372.

Blaese, R. M.，Culver, K.W.，Anderson, W.F.，Nienhuis, A.，Dunbar, C.，Chang, L.，Mullen, C.，Carter, C.，Leitman, S.，Berger, M.，et al.（1993）.Treatment of Severe Combined Immunodeficiency Disease（SCID）due to Adenosine Deaminase Deficiency with CD34+Selected Autologous Peripheral Blood Cells Transduced with a Human ADA Gene（Amendment）.National Institutes of Health.Hum Gene Ther 4，521-527.

Blaese, R. M.，Culver, K.W.，Miller, A.D.，Carter, C.S.，Fleisher, T.，Clerici, M.，Shearer, G.，Chang, L.，Chiang, Y.，Tolstoshev, P.，et al.（1995）.T Lymphocyte-Directed Gene Therapy forADA−SCID：Initial Trial Results After 4 Years.Science 270，475-480.

Bryant, L. M.，Christopher, D.M.，Giles, A.R.，Hinderer, C.，Rodriguez, J.L.，Smith, J.B.，Traxler, E.A.，Tycko, J.，Wojno, A.P.，and Wilson, J.M.（2013）.Lessons Learned from the Clinical Development and Market Authorization of Glybera.Hum Gene Ther Clin Dev 24，55-64.

Bunn, H. F.（1997）.Pathogenesis and Treatment of Sickle Cell Disease.N Engl J Med 337，762-769.

Cepko, C. L.，Roberts, B.E.，and Mulligan, R.C.（1984）.Construction and applications of a highly transmissible murine retrovirus shuttle vector.Cell 37，1053-1062.

Cohen, S. N.（2013）.DNA cloning：A personal view after 40 years.Proc Natl Acad Sci USA 110，15521-15529.

Cohen, S. N.，Chang, A.C.Y.，Boyer, H.W.，and Helling, R.B.（1973）.Construction of Biologically Functional Bacterial Plasmids In Vitro.Proc Natl Acad Sci USA 70，3240-3244.

Cuthbert, A. W.，Halstead, J.，Ratcliff, R.，Colledge, W.H.，and Evans, M.J.（1995）.The genetic advantage hypothesis in cystic fbrosis heterozygotes：a murine study.J Physiol 482，449-454.

Dolgin, E.（2015）. The myopia boom.Nature 519.

Frank, K. M.，Hogarth, D.K.，Miller, J.L.，Mandal, S.，Mease, P.J.，Samulski, R.J.，Weisgerber, G.A.，and Hart, J.（2009）.Investigation of the Cause of Death in a Gene-Therapy Trial.N Engl J Med 361，161-169.

Friedmann, T.，and Roblin, R.（1972）. Gene Therapy for Human Genetic Disease?Science 175，949-955.

Gabriel, S. E.，Brigman, K.N.，Koller, B.H.，Boucher, R.C.，and Stutts, M.J.（1994）.Cystic fbrosis heterozygote resistance to cholera toxin in the cystic fbrosis mouse model.Science 266，107-109.

Hacein-Bey-Abina, S.，Garrigue, A.，Wang, G. P.，Soulier, J.，Lim, A.，Morillon, E.，Clappier, E.，Caccavelli, L.，Delabesse, E.，Beldjord, K.，et al.（2008）.Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1.J Clin Invest 118，3132-3142.

Hütter, G.，Bodor, J.，Ledger, S.，Boyd, M.，Millington, M.，Tsie, M.，and Symonds, G.（2015）.CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape.Viruses 7，4186-4203.

Hütter, G.，Nowak, D.，Mossner, M.，Ganepola, S.，Müßig, A.，Allers, K.，Schneider, T.，Hofmann, J.，Kücherer, C.，Blau, O.，et al.（2009）.Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation.N Engl J Med 360，692-698.

Rees, D. C.，Williams, T.N.，and Gladwin, M.T.（2010）.Sickle-cell disease.Lancet 376，2018-2031.

Wirth, T.，Parker, N.，and Ylä-Herttuala, S.（2013）.History of gene therapy.Gene 525，162-169.

03 黄金手指

Bibikova, M.，Golic, M.，Golic, K. G.，and Carroll, D.（2002）.Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-fnger nucleases.Genetics 161，1169-1175.

Chandrasegaran, S.，and Carroll, D.（2016）. Origins of Programmable Nucleases for Genome Engineering.J Mol Biol 428，963-989.

Cheng, L.，Blazar, B.，High, K.，and Porteus, M.（2011）. Zinc fngers hit off target.Nat Med 17，1192-1193.

Churchill, M. E.，Tullius, T.D.，and Klug, A.（1990）.Mode of interaction of the zinc fnger protein TFIIIA with a 5S RNA gene of Xenopus.Proc Natl Acad Sci USA 87，5528-5532.

Doyon, Y.，Vo, T. D.，Mendel, M.C.，Greenberg, S.G.，Wang, J.，Xia, D.F.，Miller, J.C.，Urnov, F.D.，Gregory, P.D.，and Holmes, M.C.（2011）.Enhancing zinc-fnger-nuclease activity with improved obligate heterodimeric architectures.Nat Meth 8，74-79.

Engelke, D. R.，Ng, S.-Y.，Shastry, B.S.，and Roeder, R.G.（1980）.Specifc interaction of a purifed transcription factor with an internal control region of 5S RNA genes.Cell 19，717-728.

Ginsberg, A. M.，King, B.O.，and Roeder, R.G.（1984）.Xenopus 5S gene transcription factor, TFIIIA：Characterization of a cDNA clone and measurement of RNA levels throughout development.Cell 39，479-489.

Kandavelou, K.，Mani, M.，Durai, S.，and Chandrasegaran, S.（2005）.'Magic'scissors for genome surgery. Nat Biotech 23，686-687.

Kim, Y. G.，Cha, J.，and Chandrasegaran, S.（1996）.Hybrid restriction enzymes：zinc fnger fusions to Fok I cleavage domain.Proc Natl Acad Sci USA 93，1156-1160.

Klug, A.（2010）. The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation.Annu Rev Biochem 79，213-231.

Klug, A.，and Rhodes, D.（1987）. Zinc Fingers：A Novel Protein Fold for Nucleic Acid Recognition.Cold Spring Harb Symp Quant Biol 52，473-482.

Lu, T. K.，Chandrasegaran, S.，and Hodak, H.（2016）.The Era of Synthetic Biology and Genome Engineering：Where No Man Has Gone Before.J Mol Biol 428，835-836.

Miller, J. C.，Holmes, M.C.，Wang, J.，Guschin, D.Y.，Lee, Y.-L.，Rupniewski, I.，Beausejour, C.M.，Waite, A.J.，Wang, N.S.，Kim, K.A.，et al.（2007）.An improved zinc-fnger nuclease architecture for highly specifc genome editing.Nat Biotech 25，778-785.

Moore, M.，Choo, Y.，and Klug, A.（2001）. Design of polyzinc finger peptides with structured linkers.Proc Natl Acad Sci USA 98，1432-1436.

Porteus, M. H.，and Baltimore, D.（2003）.Chimeric Nucleases Stimulate Gene Targeting in Human Cells.Science 300，763-763.

Tebas, P.，Stein, D.，Tang, W. W.，Frank, I.，Wang, S.Q.，Lee, G.，Spratt, S.K.，Surosky, R.T.，Giedlin, M.A.，Nichol, G.，et al.（2014）.Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV.N Engl J Med 370，901-910.

Walker, F. O.（2007）.Huntington's disease.Lancet 369，218-228.

Watson, J. D.，Baker, T.A.，Bell, S.P.，Gann, A.，Levine, M.，and Losick, R.（2004）.Molecular Biology of the Gene（Pearson Benjamin Cummings）.

04 编程时代

Barrangou, R.，Fremaux, C.，Deveau, H.，Richards, M.，Boyaval, P.，Moineau, S.，Romero, D. A.，and Horvath, P.（2007）.CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes.Science 315，1709-1712.

Boch, J.，and Bonas, U.（2010）. Xanthomonas AvrBs3 Family-Type III Effectors：Discovery and Function.Annual Review of Phytopathology 48，419-436.

Boch, J.，Scholze, H.，Schornack, S.，Landgraf, A.，Hahn, S.，Kay, S.，Lahaye, T.，Nickstadt, A.，and Bonas, U.（2009）. Breaking the Code of DNA Binding Specifcity of TAL-Type III Effectors.Science 326，1509-1512.

Büttner, D.，and Bonas, U.（2002）.NEW EMBO MEMBER’S REVIEW：Getting across—bacterial type III effector proteins on their way to the plant cell.EMBO J 21，5313-5322.

Cathomen, T.，and Keith Joung, J.（2008）. Zinc-finger Nucleases：The Next Generation Emerges.Mol Ther 16，1200-1207.

Cong, L.，Ran, F. A.，Cox, D.，Lin, S.，Barretto, R.，Habib, N.，Hsu, P.D.，Wu, X.，Jiang, W.，Marraffni, L.A.，et al.（2013）.Multiplex Genome Engineering Using CRISPR/Cas Systems.Science 339，819-823.

Egelie, K. J.，Graff, G.D.，Strand, S.P.，and Johansen, B.（2016）.The emerging patent landscape of CRISPR-Cas gene editing technology.Nat Biotech 34，1025-1031.

Fellmann, C.，Gowen, B. G.，Lin, P.-C.，Doudna, J.A.，and Corn, J.E.（2017）.Cornerstonesof CRISPR-Cas in drug discovery and therapy.Nat Rev Drug Discov 16，89-100.

Foley, J. E.，Yeh, J.-R.J.，Maeder, M.L.，Reyon, D.，Sander, J.D.，Peterson, R.T.，and Joung, J.K.（2009）.Rapid Mutation of Endogenous Zebrafsh Genes Using Zinc Finger Nucleases Made by Oligomerized Pool ENgineering（OPEN）.PLoS ONE 4，e4348.

Jinek, M.，Chylinski, K.，Fonfara, I.，Hauer, M.，Doudna, J. A.，and Charpentier, E.（2012）.A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity.Science 337，816-821.

Jinek, M.，East, A.，Cheng, A.，Lin, S.，Ma, E.，and Doudna, J.（2013）. RNA-programmed genome editing in human cells.eLife 2，e00471.

Kay, S.，Hahn, S.，Marois, E.，Hause, G.，and Bonas, U.（2007）. A Bacterial Effector Acts as a Plant Transcription Factor and Induces a Cell Size Regulator.Science 318，648-651.

Kupecz, A.（2014）. Who owns CRISPR-Cas9 in Europe?Nat Biotech 32，1194-1196.

Lander, Eric S.（2016）. The Heroes of CRISPR.Cell 164，18-28.

Maeder, M. L.，Thibodeau-Beganny, S.，Osiak, A.，Wright, D.A.，Anthony, R.M.，Eichtinger, M.，Jiang, T.，Foley, J.E.，Winfrey, R.J.，Townsend, J.A.，et al.（2008）.Rapid“open-source”engineering of customized zinc-fnger nucleases for highly effcient gene modifcation.Mol Cell 31，294-301.

Mali, P.，Yang, L.，Esvelt, K. M.，Aach, J.，Guell, M.，DiCarlo, J.E.，Norville, J.E.，and Church, G.M.（2013）.RNA-Guided Human Genome Engineering via Cas9.Science 339，823-826.

Miller, J. C.，Tan, S.，Qiao, G.，Barlow, K.A.，Wang, J.，Xia, D.F.，Meng, X.，Paschon, D.E.，Leung, E.，Hinkley, S.J.，et al.（2011）.A TALE nuclease architecture for efficient genome editing.Nat Biotech 29，143-148.

Mojica, F. J.M.，Díez-Villaseñor, C.s.，García-Martínez, J.，and Soria, E.（2005）.Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements.J Mol Evol 60，174-182.

Mojica, F. J.M.，and Rodriguez-Valera, F.（2016）.The discovery of CRISPR in archaea and bacteria.FEBS J 283，3162-3169.

Moscou, M. J.，and Bogdanove, A.J.（2009）.A Simple Cipher Governs DNA Recognition by TAL Effectors.Science 326，1501-1501.

Reardon, S.（2016）. CRISPR heavyweights battle in US patent court.Nature 540.

Römer, P.，Hahn, S.，Jordan, T.，Strauß，T.，Bonas, U.，and Lahaye, T.（2007）.Plant Pathogen Recognition Mediated by Promoter Activation of the Pepper Bs3 Resistance Gene.Science 318，645-648.

Sander, J. D.，Dahlborg, E.J.，Goodwin, M.J.，Cade, L.，Zhang, F.，Cifuentes, D.，Curtin, S.J.，Blackburn, J.S.，Thibodeau-Beganny, S.，Qi, Y.，et al.（2011）.Selection-Free Zinc-Finger Nuclease Engineering by Context-Dependent Assembly（CoDA）.Nat Meth 8，67-69.

Sherkow, J. S.（2015）.Law, history and lessons in the CRISPR patent confict.Nat Biotech 33，256-257.

Van den Ackerveken, G.，Marois, E.，and Bonas, U.（1996）. Recognition of the Bacterial Avirulence Protein AvrBs3 Occurs inside the Host Plant Cell.Cell 87，1307-1316.

Zhang, F.，Cong, L.，Lodato, S.，Kosuri, S.，Church, G. M.，and Arlotta, P.（2011）.Effcient construction of sequence-specifc TAL effectors for modulating mammalian transcription.Nat Biotech 29，149-153.

05 未来，和未来的未来

Bosley, K. S.，Botchan, M.，Bredenoord, A.L.，Carroll, D.，Charo, R.A.，Charpentier, E.，Cohen, R.，Corn, J.，Doudna, J.，Feng, G.，et al.（2015）.CRISPR germline engineering[mdash]the community speaks.Nat Biotech 33，478-486.

Cyranoski, D.（2016）. Chinese scientists to pioneer frst human CRISPR trial.Nature 535.

Demorest, Z. L.，Coffman, A.，Baltes, N.J.，Stoddard, T.J.，Clasen, B.M.，Luo, S.，Retterath, A.，Yabandith, A.，Gamo, M.E.，Bissen, J.，et al.（2016）.Direct stacking of sequence-specifc nuclease-induced mutations to produce high oleic and low linolenic soybean oil.BMC Plant Biol 16，225.

Evitt, N. H.，Mascharak, S.，and Altman, R.B.（2015）.Human Germline CRISPR-Cas Modifcation：Toward a Regulatory Framework.Am J Bioeth 15，25-29.

Hildt, E.（2016）. Human Germline Interventions-Think First.Front Genet 7，81.

LaBarbera, A. R.（2016）.Proceedings of the International Summit on Human Gene Editing：a global discussion—Washington, D.C.，December 1-3，2015.J Assist Reprod Genet 33，1123-1127.

Ledford, H.（2016）. Gene-editing surges as US rethinks regulations.Nature 532.

Liang, P.，Xu, Y.，Zhang, X.，Ding, C.，Huang, R.，Zhang, Z.，Lv, J.，Xie, X.，Chen, Y.，Li, Y.，et al.（2015）. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes.Protein Cell 6，363-372.

Marx, V.（2012）. Genome-editing tools storm ahead.Nat Meth 9，1055-1059.

Miller, H. I.（2015）.Recasting Asilomar's lessons for human germline editing.Nat Biotech 33，1132-1134.

Polymeropoulos, E. T.，Plouffe, D.，LeBlanc, S.，Elliott, N.G.，Currie, S.，and Frappell, P.B.（2014）.Growth hormone transgenesis and polyploidy increase metabolic rate, alter the cardiorespiratory response and influence HSP expression in response to acute hypoxia in Atlantic salmon（Salmo salar）yolk-sac alevins.J Exp Biol 217，2268-2276.

Reardon, S.（2015）. Leukaemia success heralds wave of gene-editing therapies.Nature 527.

Shen, H.（2013）. CRISPR technology leaps from lab to industry.Nature.

Stoddard, T. J.，Clasen, B.M.，Baltes, N.J.，Demorest, Z.L.，Voytas, D.F.，Zhang, F.，and Luo, S.（2016）.Targeted Mutagenesis in Plant Cells through Transformation of Sequence-Specifc Nuclease mRNA.PLoS ONE 11，e0154634.

Travis, J.（2015）. Germline editing dominates DNA summit.Science 350，1299-1300.

Waltz, E.（2016）. Gene-edited CRISPR mushroom escapes US regulation.Nature 532.