Genetic circuits to engineer tissues with alternative functions.

C P Healy, T L Deans
Author Information
  1. C P Healy: Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112 USA.
  2. T L Deans: Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112 USA.

Abstract

Persistent and complex problems arising with respect to human physiology and pathology have led to intense investigation into therapies and tools that permit more targeted outcomes and biomimetic responses to pathological conditions. A primary goal in mammalian synthetic biology is to build genetic circuits that exert fine control over cell behavior for next-generation biomedical applications. In pursuit of this, synthetic biologists have engineered cells endowed with genetic circuits with sensor that are capable of reacting to a variety of stimuli and responding with targeted behavior. Here, we highlight how synthetic biology approaches are being used to program cells with novel functions for therapeutic applications, and how they can be used in stem cells to improve differentiation outcomes. These approaches open the possibilities for engineering synthetic tissues for employing personalized medicine and to develop next-generation biomedical therapies.

References

  1. Nature. 2000 Jan 20;403(6767):335-8 [PMID: 10659856]
  2. Nature. 2000 Jan 20;403(6767):339-42 [PMID: 10659857]
  3. Nature. 2000 Nov 16;408(6810):313-9 [PMID: 11099031]
  4. Am J Physiol Endocrinol Metab. 2002 Apr;282(4):E873-9 [PMID: 11882507]
  5. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6355-60 [PMID: 15096621]
  6. Mol Cell Biol. 2005 Feb;25(4):1215-27 [PMID: 15684376]
  7. Physiol Rev. 2005 Apr;85(2):635-78 [PMID: 15788707]
  8. Cell. 2005 Sep 23;122(6):947-56 [PMID: 16153702]
  9. J Mol Biol. 2006 Jan 27;355(4):619-27 [PMID: 16330045]
  10. Mol Syst Biol. 2006;2:2006.0028 [PMID: 16738572]
  11. Cell. 2006 Aug 25;126(4):663-76 [PMID: 16904174]
  12. Nat Biotechnol. 2007 Jul;25(7):795-801 [PMID: 17515909]
  13. Cell. 2007 Jul 27;130(2):363-72 [PMID: 17662949]
  14. Science. 2007 Dec 21;318(5858):1917-20 [PMID: 18029452]
  15. Blood. 2008 Apr 15;111(8):4375-85 [PMID: 18258797]
  16. Science. 2008 Aug 1;321(5889):699-702 [PMID: 18276851]
  17. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3238-43 [PMID: 18299577]
  18. Cell Stem Cell. 2007 Jun 7;1(1):39-49 [PMID: 18371333]
  19. Cell. 2008 Jun 13;133(6):947-8 [PMID: 18555769]
  20. Nature. 2008 Oct 2;455(7213):627-32 [PMID: 18754011]
  21. Nature. 2009 Jan 15;457(7227):309-12 [PMID: 19148099]
  22. Chem Biol. 2009 Mar 27;16(3):287-97 [PMID: 19318210]
  23. Curr Opin Biotechnol. 2009 Oct;20(5):537-44 [PMID: 19879127]
  24. Nat Biotechnol. 2009 Dec;27(12):1139-50 [PMID: 20010597]
  25. Bioessays. 2010 Apr;32(4):332-45 [PMID: 20238390]
  26. Nat Rev Genet. 2010 May;11(5):367-79 [PMID: 20395970]
  27. Curr Opin Chem Biol. 2011 Jun;15(3):414-20 [PMID: 21470897]
  28. Science. 2011 Jun 24;332(6037):1565-8 [PMID: 21700876]
  29. Mol Syst Biol. 2011 Aug 16;7:521 [PMID: 21847113]
  30. Science. 2011 Sep 2;333(6047):1248-52 [PMID: 21885773]
  31. Curr Opin Biotechnol. 2012 Oct;23(5):689-94 [PMID: 22237017]
  32. Curr Opin Biotechnol. 2012 Oct;23(5):703-11 [PMID: 22305476]
  33. Nucleic Acids Res. 2012 Jun;40(11):5180-7 [PMID: 22323524]
  34. Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5850-5 [PMID: 22454498]
  35. Annu Rev Biomed Eng. 2012;14:155-78 [PMID: 22577777]
  36. Curr Opin Chem Biol. 2012 Aug;16(3-4):355-61 [PMID: 22609142]
  37. Nature. 2012 Jul 5;487(7405):123-7 [PMID: 22722847]
  38. Curr Opin Chem Biol. 2012 Aug;16(3-4):345-54 [PMID: 22819494]
  39. Cell. 2012 Aug 3;150(3):647-58 [PMID: 22863014]
  40. Nat Biotechnol. 2012 Oct;30(10):991-6 [PMID: 22983089]
  41. Trends Biotechnol. 2013 Mar;31(3):155-68 [PMID: 23245728]
  42. Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):141-6 [PMID: 23248313]
  43. Nat Biotechnol. 2013 May;31(5):448-52 [PMID: 23396014]
  44. ACS Synth Biol. 2013 Feb 15;2(2):72-82 [PMID: 23526588]
  45. Science. 2013 May 3;340(6132):599-603 [PMID: 23539178]
  46. ACS Synth Biol. 2012 Mar 16;1(3):83-8 [PMID: 23651072]
  47. ACS Synth Biol. 2012 Oct 19;1(10):451-7 [PMID: 23656184]
  48. Trends Biotechnol. 2013 Jul;31(7):397-405 [PMID: 23664777]
  49. Nature. 2013 May 30;497(7451):619-23 [PMID: 23676681]
  50. ACS Synth Biol. 2013 Dec 20;2(12):715-23 [PMID: 23763381]
  51. Curr Protoc Chem Biol. 2013;5(2):111-29 [PMID: 23839993]
  52. Cell. 2013 Jul 18;154(2):442-51 [PMID: 23849981]
  53. ACS Synth Biol. 2013 Oct 18;2(10):604-13 [PMID: 23977949]
  54. Nat Commun. 2013;4:2393 [PMID: 23999119]
  55. ACS Synth Biol. 2014 Apr 18;3(4):228-37 [PMID: 24020906]
  56. Mol Syst Biol. 2013;9:691 [PMID: 24061539]
  57. Nat Protoc. 2013 Nov;8(11):2180-96 [PMID: 24136345]
  58. Stem Cells Cloning. 2009 Dec 22;3:13-27 [PMID: 24198508]
  59. Int J Stem Cells. 2011 Jun;4(1):1-8 [PMID: 24298328]
  60. Nat Rev Mol Cell Biol. 2014 Feb;15(2):95-107 [PMID: 24434884]
  61. Curr Opin Chem Biol. 2013 Dec;17(6):910-7 [PMID: 24466575]
  62. Nat Biotechnol. 2014 Apr;32(4):347-55 [PMID: 24584096]
  63. Biotechnol J. 2014 May;9(5):597-608 [PMID: 24677719]
  64. Nat Rev Microbiol. 2014 May;12(5):381-90 [PMID: 24686414]
  65. Nat Methods. 2014 May;11(5):508-20 [PMID: 24781324]
  66. Curr Opin Biotechnol. 2014 Oct;29:146-55 [PMID: 24794536]
  67. Nat Methods. 2014 Jul;11(7):723-6 [PMID: 24797424]
  68. Mol Cell. 2014 May 22;54(4):698-710 [PMID: 24837679]
  69. FEBS Lett. 2014 Aug 1;588(15):2537-44 [PMID: 24844435]
  70. Cell Stem Cell. 2014 Aug 7;15(2):215-226 [PMID: 24931489]
  71. Mol Cell. 2014 Aug 7;55(3):397-408 [PMID: 25018017]
  72. Science. 2014 Jul 18;345(6194):1247125 [PMID: 25035496]
  73. Nat Methods. 2014 Nov;11(11):1147-53 [PMID: 25218181]
  74. Nat Methods. 2014 Dec;11(12):1261-6 [PMID: 25344638]
  75. Nat Commun. 2014 Nov 06;5:5393 [PMID: 25373919]
  76. Science. 2014 Nov 14;346(6211):1256272 [PMID: 25395541]
  77. Stem Cells Int. 2014;2014:768391 [PMID: 25431601]
  78. Sci Rep. 2014 Dec 10;4:7402 [PMID: 25492588]
  79. Nature. 2015 Jan 29;517(7536):583-8 [PMID: 25494202]
  80. World J Stem Cells. 2015 Jan 26;7(1):174-81 [PMID: 25621117]
  81. Front Cell Dev Biol. 2015 Feb 02;3:2 [PMID: 25699255]
  82. J R Soc Interface. 2015 May 6;12(106):null [PMID: 25808341]
  83. J Biol Eng. 2015 Apr 14;9:5 [PMID: 25897323]
  84. Curr Opin Chem Biol. 2015 Oct;28:29-38 [PMID: 26056952]
  85. J Biol Eng. 2015 Aug 12;9:13 [PMID: 26265937]
  86. J Mol Biol. 2016 Feb 27;428(5 Pt B):945-62 [PMID: 26334368]
  87. Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14429-35 [PMID: 26598662]
  88. Integr Biol (Camb). 2016 Apr 18;8(4):409-30 [PMID: 26705548]
  89. Nat Commun. 2016 Jan 06;7:10243 [PMID: 26732624]
  90. Cell Stem Cell. 2016 Mar 3;18(3):410-21 [PMID: 26908146]
  91. Stem Cells Int. 2016;2016:4373410 [PMID: 27057170]
  92. Nat Commun. 2016 Apr 11;7:11247 [PMID: 27063289]
  93. Curr Opin Biotechnol. 2016 Aug;40:139-148 [PMID: 27135809]
  94. Cold Spring Harb Perspect Biol. 2016 Jul 01;8(7): [PMID: 27194045]
  95. Methods Mol Biol. 2016;1416:109-22 [PMID: 27236668]
  96. Wiley Interdiscip Rev Syst Biol Med. 2016 Sep;8(5):402-22 [PMID: 27341681]
  97. Curr Stem Cell Rep. 2016;2:304-312 [PMID: 27547712]
  98. Adv Drug Deliv Rev. 2016 Oct 1;105(Pt A):20-34 [PMID: 27568463]
  99. Adv Drug Deliv Rev. 2016 Oct 1;105(Pt A):1-2 [PMID: 27653994]
  100. J Cell Biol. 2017 Jan 2;216(1):73-82 [PMID: 27932576]
  101. Angew Chem Int Ed Engl. 2017 Jun 1;56(23):6396-6419 [PMID: 27943572]
  102. Mol Ther. 2017 Jan 4;25(1):102-119 [PMID: 28129106]
  103. Mol Ther Nucleic Acids. 2016;5:e349 [PMID: 28131272]
  104. Curr Opin Biotechnol. 2017 Oct;47:59-66 [PMID: 28662442]
  105. Curr Opin Biotechnol. 2017 Oct;47:133-141 [PMID: 28750201]
  106. ACS Synth Biol. 2017 Nov 17;6(11):2014-2020 [PMID: 28776984]
  107. Science. 2018 Feb 9;359(6376): [PMID: 29439214]
  108. J Ind Microbiol Biotechnol. 2018 Jul;45(7):599-614 [PMID: 29552703]
  109. BMC Musculoskelet Disord. 2018 May 30;19(1):176 [PMID: 29848328]
  110. Nat Rev Mol Cell Biol. 2018 Aug;19(8):507-525 [PMID: 29858606]
  111. Nat Methods. 2018 Aug;15(8):611-616 [PMID: 30013045]
  112. Am J Orthop (Belle Mead NJ). 2018 Nov;47(11):null [PMID: 30517209]
  113. EMBO J. 1997 Jul 1;16(13):3965-73 [PMID: 9233806]

Grants

  1. R21 EB025413/NIBIB NIH HHS

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