Some unique living organisms produce visible light from chemical energy in a process called bioluminescence. Bioluminescent organisms express luciferase enzymes which catalyze chemical reactions in which luciferases convert their substrates and produce visible light. Different bioluminescent organisms contain different luciferase enzyme/substrate systems. For creating an assay system, genes encoding selected luciferase reporter and any protein, can be fused via cDNA synthesis and then luciferase-fused protein can be traced in living organism or in cell culture, depending on bioluminescence glowing (radiation). Besides, in a predetermined setup, progression phases of experimentally created infections of any bacteria, virus, parasite or fungus species which transfected with luciferase encoding gene can easily be traced via bioluminescence. Any bioluminescence assay system is composed from three elements: transfer of luciferase gene and injection of its substrate material to animal subject, and acquiring/processing light signals by charge coupled device (CCD) camera. In bioluminescence resonance energy transfer (BRET) system which is particularly used in protein-protein interaction (PPI) studies, closely positioned or interacting labeled-proteins give both bioluminescent and fluorescent signals. In comparison to other protein-assay techniques, bioluminescence imaging is simple, non-invasive, cost-effective and convenient technique which is promising in terms of finding more usage areas in the future. In this paper, besides a review of important studies focused on the subject, general knowledge about basic principles of bioluminescence, various bioluminescence-creating enzyme-substrate systems and bioluminescence imaging (BLI) modalities were provided.
1. Sliney DH. What is light? The visible spectrum and beyond. Eye. 2016;30:222–29.
2. Claridge E, Cotton S, Hall P, Moncrieff M. From colour to tissue histology: Physics-based interpretation of images of pigmented skin lesions. Med Image Anal. 2003;7:489–502
5. Pietrzykowska M. The roles of Lhcb1 and Lhcb2 in regulation of photosynthetic light harvesting (PhD thesis). Umea/Sweden, Umea University, 2015.
6. Avci P, Karimi M, Sadasivam M, Antunes-Melo WC, Carrasco E, Hamblin MR. In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging. Virulence. 2018;9(1):28-63.
7. Liu L, Cui G, Fang WH. Excited states and photochemistry of chromophores in the photoactive proteins explored by the combined quantum mechanical and molecular mechanical calculations. Adv Protein Chem Struct Biol. 2015;100:255-84.
9. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (editors). Molecular biology of the cell. In visualizing cells. 5th ed., New York: Garland Science, Taylor & Francis Group, 2008, p. 586-7.
10. Shimomura O. The discovery of aequorin and green fluorescent protein. J Microsc. 2005;217(Pt 1):1-15.
11. Stepanenko OV, Verkhusha VV, Kuznetsova IM, Uversky VN, Turoverov KK. Fluorescent proteins as biomarkers and biosensors: throwing color lights on molecular and cellular processes. Curr Protein Pept Sci. 2008;9(4):338-69.
12. Kim JE, Kalimuthu S, Ahn BC. In vivo cell tracking with bioluminescence imaging. Nucl Med Mol Imaging. 2015;49:3–10.
13. Mezzanotte L, van’t Root M, Karatas H, Goun EA, Löwik CWGM. In vivo molecular bioluminescence imaging: new tools and applications. Trends Biotechnol. 2017;35(7):640-52.
14. Suff N, Waddington SN. The power of bioluminescence imaging in understanding host-pathogen interactions. Methods. 2017;127:69–78
15. Tannous BA, Kim DE, Fernandez JL, Weissleder R, Breakefield XO. Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Ther. 2005;11(3):435-43.
16. Greer LF 3rd, Szalay AA. Imaging of light emission from the expression of luciferases in living cells and organisms: a review. Luminescence. 2002;17(1):43-74.
17. Kennedy HJ, Rafiq I, Pouli AE, Rutter GA. Glucose enhances insulin promoter activity in MIN6 beta-cells independently of changes in intracellular Ca2+ concentration and insulin secretion. Biochem J. 1999;342(Pt 2):275-80.
18. Xu T, Ripp S, Sayler GS, Close DM. Expression of a humanized viral 2A-mediated lux operon efficiently generates autonomous bioluminescence in human cells. PLoS One. 2014;9(5):e96347.
19. Welsh DK,... Kay SA. Luciferase. In Methods in Enzymology. 2005. https://www.sciencedirect.com/topics/neuroscience/luciferase, 28-01-2019.
20. Eun HM. Luciferase. In Enzymology Primer for Recombinant DNA Technology. 1996. https://www.sciencedirect.com/topics/neuroscience/luciferase, 28-01-2019.
21. Naumov P, Ozawa Y, Ohkubo K, Fukuzumi S. Structure and spectroscopy of oxyluciferin, the light emitter of the firefly bioluminescence. J Am Chem Soc., 2009;131 (32):11590–605.
22. Branchini BR, Southwort TL, Fontaine DM, Kohrt D, Talukder M, Michelini E et al. An enhanced chimeric firefly luciferase-inspired enzyme for ATP detection and bioluminescence reporter and imaging applications. Anal Biochem. 2015;484: 148–53.
24. Lee J, Müller F, Visser AJWG. The sensitized bioluminescence mechanism of bacterial luciferase. Photochem Photobiol. 2018;doi: 10.1111/php.13063(Epub ahead of print).
25. Bessho-Uehara M, Oba Y. Identification and characterization of the Luc2-type luciferase in the Japanese firefly, Luciola parvula, involved in a dim luminescence in immobile stages. Luminescence. 2017;32(6):924-31.
26. Stacer AC, Nyati S, Moudgil P, Iyengar R, Luker KE, Rehemtulla A et al. NanoLuc reporter for dual luciferase imaging in living animals. Mol Imaging. 2013;12(7):1-13.
27. Nakajima Y, Kobayashi K, Yamagishi K, Enomoto T, Ohmiya Y. cDNA cloning and characterization of a secreted luciferase from the luminous Japanese ostracod, Cypridina noctiluca. Biosci Biotechnol Biochem. 2004;68(3):565-70.
28. Gupta RK, Patterson SS, Ripp S, Simpson ML, Sayler GS. Expression of the Photorhabdus luminescens lux genes (luxA, B, C, D, and E) in Saccharomyces cerevisiae. FEMS Yeast Res. 2003;4(3):305-13.
29. Yang G, Kramer MG, Fernandez-Ruiz V, Kawa MP, Huang X, Liu Z et al. Development of endothelial-specific single inducible lentiviral vectors for genetic engineering of endothelial progenitor cells. Sci Rep. 2015;5:17166.
30. Sugihara K, Park HM, Muramatsu T. In vivo gene electroporation confers strong transient expression of foreign genes in the chicken testis. Poult Sci. 2000;79(8): 1116–9.
31. March KL, Woody M, Mehdi K, Zipes DP, Brantly M, Trapnell BC. Efficient in vivo catheter-based pericardial gene transfer mediated by adenoviral vectors. Clin Cardiol. 1999;22(1 Suppl 1):I23-9.
32. Lipshutz GS, Gruber CA, Cao Y, Hardy J, Contag CH, Gaensler KM. In utero delivery of adeno-associated viral vectors: intraperitoneal gene transfer produces long-term expression. Mol Ther. 2001;3(3):284–92.
33. Lau CP, Wong KC, Huang L, Li G, Tsui SK, Kumta SM. A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone. Connect Tissue Res. 2015;56(6):493-503.
34. Milocco A, Conroy S, Popovichev S, Sergienko G, Huber A. Neutron radiation damage in ccd cameras at joint european torus (jet). Radiat Prot Dosimetry. 2018;180(1-4):109-114.
36. Feng J, Qin C, Jia K, Zhu S, Yang X, Tian J. Bioluminescence Tomography Imaging In Vivo: Recent Advances. IEEE journal of selected topics in quantum electronics. 2012;18(4).
37. El Khamlichi C, Reverchon-Assadi F, Hervouet-Coste N, Blot L, Reiter E, Morisset-Lopez S. Bioluminescence resonance energy transfer as a method to study protein-protein interactions: Application to G protein coupled receptor biology. Molecules. 2019;24(3):pii:E537.
38. Schuster M, Kilaru S, Guo M, Sommerauer M, Lin C, Steinberg G. Red fluorescent proteins for imaging Zymoseptoria tritici during invasion of wheat. Fungal Genet Biol. 2015;79:132-40.
39. Ihara K, Nishimura T, Fukuda T, Ookura T, Nishimori K. Generation of Venus reporter knock-in mice revealed MAGI-2 expression patterns in adult mice. Gene Expr Patterns. 2012;12(3-4):95-101.
40. De A, Ray P, Loening AM, Gambhir SS. BRET3: a red-shifted bioluminescence resonance energy transfer (BRET)-based integrated platform for imaging protein-protein interactions from single live cells and living animals. FASEB J. 2009;23(8):2702–09.
41. Goyet E, Bouquier N, Ollendorff V, Perroy J. Fast and high resolution single-cell BRET imaging. Sci Rep. 2016;6:28231.
42. De A, Jasani A, Arora R, Gambhir SS. Evolution of BRET biosensors from live cell to tissue-scale in vivo imaging. Front Endocrinol (Lausanne). 2013;4:131.
43. Gandia J, Galino J, Amaral OB, Soriano A, Lluís C, Franco R et al. Detection of higher-order G protein-coupled receptor oligomers by a combined BRET-BiFC technique. FEBS Lett. 2008;582(20):2979-84.
44. Urizar E, Yano H, Kolster R, Galés C, Lambert N, Javitch JA. CODA-RET reveals functional selectivity as a result of GPCR heteromerization. Nat Chem Biol. 2011;7(9):624-30.
45. Niswender CM, Jones CK, Lin X, Bubser M, Thompson Gray A, Blobaum AL et al. Development and antiparkinsonian activity of VU0418506, a selective positive allosteric modulator of metabotropic glutamate receptor 4 homomers without activity at mGlu2/4 heteromers. ACS Chem Neurosci. 2016;7(9):1201-11.
46. Rebois RV, Robitaille M, Pétrin D, Zylbergold P, Trieu P, Hébert TE. Combining protein complementation assays with resonance energy transferto detect multipartner protein complexes in living cells. Methods. 2008;45:214–18.
47. Waadt R, Schlücking K, Schroeder JI, Kudla J. Protein fragment bimolecular fluorescence complementation analyses for the in vivo study of protein-protein interactions and cellular protein complex localizations. Methods Mol Biol. 2014;1062:629–58.
48. Banaszynski LA, Liu CW, Wandless TJ. Characterization of the FKBP.rapamycin.FRB ternary complex. J Am Chem Soc. 2005;127(13):4715-21.
49. Dragulescu-Andrasi A, Chan CT, De A, Massoud TF, Gambhir SS. Bioluminescence resonance energy transfer (BRET) imaging of protein-protein interactions within deep tissues of living subjects. Proc Natl Acad Sci U S A. 2011;108(29):12060-5.
50. Kang JH, Chung JK. Molecular-genetic imaging based on reporter gene expression. J Nucl Med. 2008;49(Suppl 2):164S-79S.
51. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (editors). Molecular biology of the cell. In visualizing cells. 5th ed., New York: Garland Science, Taylor & Francis Group, 2008, p.582-583.
52. Wang H, Cao F, De A, Cao Y, Contag C, Gambhir SS et al. Trafficking mesenchymal stem cell engraftment and differentiation in tumor-bearing mice by bioluminescence imaging. Stem Cells. 2009;27(7):1548-58.
53. Zinn KR, Chaudhuri TR, Szafran AA, O'Quinn D, Weaver C, Dugger K et al. Noninvasive bioluminescence imaging in small animals. ILAR J. 2008;49(1):103-15.
54. Hong H, Yang Y, Zhang Y, Cai W. Non-invasive cell tracking in cancer and cancer therapy. Curr Top Med Chem. 2010;10(12):1237-48.
55. Jones L, Richmond J, Evans K, Carol H, Jing D, Kurmasheva RT et al. Bioluminescence Imaging Enhances Analysis of Drug Responses in a Patient-Derived Xenograft Model of Pediatric ALL. Clin Cancer Res. 2017;23(14):3744-55.
56. Sharifian S, Homaei A, Hemmati R, B Luwor R, Khajeh K. The emerging use of bioluminescence in medical research. Biomed Pharmacother. 2018;101:74-86.
57. Li Y, Liu M, Cui J, Yang K, Zhao L, Gong M. Hepa1-6-FLuc cell line with the stable expression of firefly luciferase retains its primary properties with promising bioluminescence imaging ability. Oncol Lett. 2018;15(5):6203-10.
58. Kanno A, Ozawa T, Umezawa Y. Genetically encoded optical probe for detecting release of proteins from mitochondria toward cytosol in living cells and mammals. Anal Chem. 2006;78(23):8076-81.
59. Bacart J, Corbel C, Jockers R, Bach S, Couturier C. The BRET technology and its application to screening assays. Biotechnol J. 2008;3(3):311-24.
60. Pfleger KD, Eidne KA. Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET). Nat Methods. 2006;3(3):165-74.
Biyolüminesans ışıma ve biyolüminesans görüntüleme tekniklerinin moleküler biyoloji araştırmaları bakımından önemi
Year 2019,
Volume: 44 Issue: 4, 1473 - 1483, 29.12.2019
Canlı bünyesinde meydana gelen reaksiyonlar sonucunda kimyasal enerjiden görünür ışık üretilmesine ve buna bağlı olarak meydana gelen ışımaya biyolüminesans ışıma denir. Biyolminesans gösteren organizmaların sentezledikleri lusiferaz enzimler ve kimyasal dönüşümlerini katalizledikleri ilgili substratların oluşturdukları reaksiyonlar neticesinde biyolüminesans ışıma meydana gelmektedir. Farklı canlı türlerinde çeşitli lusiferaz enzimleri bulunmaktadır. Lusiferaz enzimlerden seçilecek olan birini kodlayan reporter gen, cDNA aracılığıyla herhangi bir proteini kodlayan genle kaynaştırılmak suretiyle, ilgili proteinin lokasyonu veya etkileşimleri in vivo olarak izlenebilmektedir. İlgilenilen virüs, bakteri, parazit ve maya türlerine aktarılan lusiferaz enzim genleri sayesinde, bu türlerin oluşturdukları enfeksiyonların seyir süreçleri izlenebilmektedir. İzleme düzeneği, ilgili denek hayvana lusiferaz geninin aktarılması, hayvana substratın enjekte edilmesi ve CCD kamera (foton-elektron etkileşimli kamera) ile izlemenin yapılması basamaklarından oluşmaktadır. Özellikle protein-protein etkileşim çalışmalarında kullanılan BRET (biyolüminesans ışımaya dayalı rezonans enerji transferi) tekniği ile biyolüminesans ve floresan ışımalar bir arada izlenebilmektedir. Diğer protein saptama/izleme teknikleri ile kıyaslandığında in vivo biyolüminesans görüntüleme denek hayvana girişimde bulunmayı gerektirmeyen, basit, ucuz ve oldukça elverişli bir tekniktir. Bu çalışmada biyolüminesans ışımanın temel prensipleri, biyolüminesans ışıma üreten enzim-substrat sistemleri ve biyolüminesans ışımaya dayalı çeşitli in vivo izleme düzenekleri hakkında genel bilgiler verilmiş ve bu konularla ilgili önemli çalışmaların sonuçları derlenmiştir.
1. Sliney DH. What is light? The visible spectrum and beyond. Eye. 2016;30:222–29.
2. Claridge E, Cotton S, Hall P, Moncrieff M. From colour to tissue histology: Physics-based interpretation of images of pigmented skin lesions. Med Image Anal. 2003;7:489–502
5. Pietrzykowska M. The roles of Lhcb1 and Lhcb2 in regulation of photosynthetic light harvesting (PhD thesis). Umea/Sweden, Umea University, 2015.
6. Avci P, Karimi M, Sadasivam M, Antunes-Melo WC, Carrasco E, Hamblin MR. In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging. Virulence. 2018;9(1):28-63.
7. Liu L, Cui G, Fang WH. Excited states and photochemistry of chromophores in the photoactive proteins explored by the combined quantum mechanical and molecular mechanical calculations. Adv Protein Chem Struct Biol. 2015;100:255-84.
9. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (editors). Molecular biology of the cell. In visualizing cells. 5th ed., New York: Garland Science, Taylor & Francis Group, 2008, p. 586-7.
10. Shimomura O. The discovery of aequorin and green fluorescent protein. J Microsc. 2005;217(Pt 1):1-15.
11. Stepanenko OV, Verkhusha VV, Kuznetsova IM, Uversky VN, Turoverov KK. Fluorescent proteins as biomarkers and biosensors: throwing color lights on molecular and cellular processes. Curr Protein Pept Sci. 2008;9(4):338-69.
12. Kim JE, Kalimuthu S, Ahn BC. In vivo cell tracking with bioluminescence imaging. Nucl Med Mol Imaging. 2015;49:3–10.
13. Mezzanotte L, van’t Root M, Karatas H, Goun EA, Löwik CWGM. In vivo molecular bioluminescence imaging: new tools and applications. Trends Biotechnol. 2017;35(7):640-52.
14. Suff N, Waddington SN. The power of bioluminescence imaging in understanding host-pathogen interactions. Methods. 2017;127:69–78
15. Tannous BA, Kim DE, Fernandez JL, Weissleder R, Breakefield XO. Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Ther. 2005;11(3):435-43.
16. Greer LF 3rd, Szalay AA. Imaging of light emission from the expression of luciferases in living cells and organisms: a review. Luminescence. 2002;17(1):43-74.
17. Kennedy HJ, Rafiq I, Pouli AE, Rutter GA. Glucose enhances insulin promoter activity in MIN6 beta-cells independently of changes in intracellular Ca2+ concentration and insulin secretion. Biochem J. 1999;342(Pt 2):275-80.
18. Xu T, Ripp S, Sayler GS, Close DM. Expression of a humanized viral 2A-mediated lux operon efficiently generates autonomous bioluminescence in human cells. PLoS One. 2014;9(5):e96347.
19. Welsh DK,... Kay SA. Luciferase. In Methods in Enzymology. 2005. https://www.sciencedirect.com/topics/neuroscience/luciferase, 28-01-2019.
20. Eun HM. Luciferase. In Enzymology Primer for Recombinant DNA Technology. 1996. https://www.sciencedirect.com/topics/neuroscience/luciferase, 28-01-2019.
21. Naumov P, Ozawa Y, Ohkubo K, Fukuzumi S. Structure and spectroscopy of oxyluciferin, the light emitter of the firefly bioluminescence. J Am Chem Soc., 2009;131 (32):11590–605.
22. Branchini BR, Southwort TL, Fontaine DM, Kohrt D, Talukder M, Michelini E et al. An enhanced chimeric firefly luciferase-inspired enzyme for ATP detection and bioluminescence reporter and imaging applications. Anal Biochem. 2015;484: 148–53.
24. Lee J, Müller F, Visser AJWG. The sensitized bioluminescence mechanism of bacterial luciferase. Photochem Photobiol. 2018;doi: 10.1111/php.13063(Epub ahead of print).
25. Bessho-Uehara M, Oba Y. Identification and characterization of the Luc2-type luciferase in the Japanese firefly, Luciola parvula, involved in a dim luminescence in immobile stages. Luminescence. 2017;32(6):924-31.
26. Stacer AC, Nyati S, Moudgil P, Iyengar R, Luker KE, Rehemtulla A et al. NanoLuc reporter for dual luciferase imaging in living animals. Mol Imaging. 2013;12(7):1-13.
27. Nakajima Y, Kobayashi K, Yamagishi K, Enomoto T, Ohmiya Y. cDNA cloning and characterization of a secreted luciferase from the luminous Japanese ostracod, Cypridina noctiluca. Biosci Biotechnol Biochem. 2004;68(3):565-70.
28. Gupta RK, Patterson SS, Ripp S, Simpson ML, Sayler GS. Expression of the Photorhabdus luminescens lux genes (luxA, B, C, D, and E) in Saccharomyces cerevisiae. FEMS Yeast Res. 2003;4(3):305-13.
29. Yang G, Kramer MG, Fernandez-Ruiz V, Kawa MP, Huang X, Liu Z et al. Development of endothelial-specific single inducible lentiviral vectors for genetic engineering of endothelial progenitor cells. Sci Rep. 2015;5:17166.
30. Sugihara K, Park HM, Muramatsu T. In vivo gene electroporation confers strong transient expression of foreign genes in the chicken testis. Poult Sci. 2000;79(8): 1116–9.
31. March KL, Woody M, Mehdi K, Zipes DP, Brantly M, Trapnell BC. Efficient in vivo catheter-based pericardial gene transfer mediated by adenoviral vectors. Clin Cardiol. 1999;22(1 Suppl 1):I23-9.
32. Lipshutz GS, Gruber CA, Cao Y, Hardy J, Contag CH, Gaensler KM. In utero delivery of adeno-associated viral vectors: intraperitoneal gene transfer produces long-term expression. Mol Ther. 2001;3(3):284–92.
33. Lau CP, Wong KC, Huang L, Li G, Tsui SK, Kumta SM. A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone. Connect Tissue Res. 2015;56(6):493-503.
34. Milocco A, Conroy S, Popovichev S, Sergienko G, Huber A. Neutron radiation damage in ccd cameras at joint european torus (jet). Radiat Prot Dosimetry. 2018;180(1-4):109-114.
36. Feng J, Qin C, Jia K, Zhu S, Yang X, Tian J. Bioluminescence Tomography Imaging In Vivo: Recent Advances. IEEE journal of selected topics in quantum electronics. 2012;18(4).
37. El Khamlichi C, Reverchon-Assadi F, Hervouet-Coste N, Blot L, Reiter E, Morisset-Lopez S. Bioluminescence resonance energy transfer as a method to study protein-protein interactions: Application to G protein coupled receptor biology. Molecules. 2019;24(3):pii:E537.
38. Schuster M, Kilaru S, Guo M, Sommerauer M, Lin C, Steinberg G. Red fluorescent proteins for imaging Zymoseptoria tritici during invasion of wheat. Fungal Genet Biol. 2015;79:132-40.
39. Ihara K, Nishimura T, Fukuda T, Ookura T, Nishimori K. Generation of Venus reporter knock-in mice revealed MAGI-2 expression patterns in adult mice. Gene Expr Patterns. 2012;12(3-4):95-101.
40. De A, Ray P, Loening AM, Gambhir SS. BRET3: a red-shifted bioluminescence resonance energy transfer (BRET)-based integrated platform for imaging protein-protein interactions from single live cells and living animals. FASEB J. 2009;23(8):2702–09.
41. Goyet E, Bouquier N, Ollendorff V, Perroy J. Fast and high resolution single-cell BRET imaging. Sci Rep. 2016;6:28231.
42. De A, Jasani A, Arora R, Gambhir SS. Evolution of BRET biosensors from live cell to tissue-scale in vivo imaging. Front Endocrinol (Lausanne). 2013;4:131.
43. Gandia J, Galino J, Amaral OB, Soriano A, Lluís C, Franco R et al. Detection of higher-order G protein-coupled receptor oligomers by a combined BRET-BiFC technique. FEBS Lett. 2008;582(20):2979-84.
44. Urizar E, Yano H, Kolster R, Galés C, Lambert N, Javitch JA. CODA-RET reveals functional selectivity as a result of GPCR heteromerization. Nat Chem Biol. 2011;7(9):624-30.
45. Niswender CM, Jones CK, Lin X, Bubser M, Thompson Gray A, Blobaum AL et al. Development and antiparkinsonian activity of VU0418506, a selective positive allosteric modulator of metabotropic glutamate receptor 4 homomers without activity at mGlu2/4 heteromers. ACS Chem Neurosci. 2016;7(9):1201-11.
46. Rebois RV, Robitaille M, Pétrin D, Zylbergold P, Trieu P, Hébert TE. Combining protein complementation assays with resonance energy transferto detect multipartner protein complexes in living cells. Methods. 2008;45:214–18.
47. Waadt R, Schlücking K, Schroeder JI, Kudla J. Protein fragment bimolecular fluorescence complementation analyses for the in vivo study of protein-protein interactions and cellular protein complex localizations. Methods Mol Biol. 2014;1062:629–58.
48. Banaszynski LA, Liu CW, Wandless TJ. Characterization of the FKBP.rapamycin.FRB ternary complex. J Am Chem Soc. 2005;127(13):4715-21.
49. Dragulescu-Andrasi A, Chan CT, De A, Massoud TF, Gambhir SS. Bioluminescence resonance energy transfer (BRET) imaging of protein-protein interactions within deep tissues of living subjects. Proc Natl Acad Sci U S A. 2011;108(29):12060-5.
50. Kang JH, Chung JK. Molecular-genetic imaging based on reporter gene expression. J Nucl Med. 2008;49(Suppl 2):164S-79S.
51. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (editors). Molecular biology of the cell. In visualizing cells. 5th ed., New York: Garland Science, Taylor & Francis Group, 2008, p.582-583.
52. Wang H, Cao F, De A, Cao Y, Contag C, Gambhir SS et al. Trafficking mesenchymal stem cell engraftment and differentiation in tumor-bearing mice by bioluminescence imaging. Stem Cells. 2009;27(7):1548-58.
53. Zinn KR, Chaudhuri TR, Szafran AA, O'Quinn D, Weaver C, Dugger K et al. Noninvasive bioluminescence imaging in small animals. ILAR J. 2008;49(1):103-15.
54. Hong H, Yang Y, Zhang Y, Cai W. Non-invasive cell tracking in cancer and cancer therapy. Curr Top Med Chem. 2010;10(12):1237-48.
55. Jones L, Richmond J, Evans K, Carol H, Jing D, Kurmasheva RT et al. Bioluminescence Imaging Enhances Analysis of Drug Responses in a Patient-Derived Xenograft Model of Pediatric ALL. Clin Cancer Res. 2017;23(14):3744-55.
56. Sharifian S, Homaei A, Hemmati R, B Luwor R, Khajeh K. The emerging use of bioluminescence in medical research. Biomed Pharmacother. 2018;101:74-86.
57. Li Y, Liu M, Cui J, Yang K, Zhao L, Gong M. Hepa1-6-FLuc cell line with the stable expression of firefly luciferase retains its primary properties with promising bioluminescence imaging ability. Oncol Lett. 2018;15(5):6203-10.
58. Kanno A, Ozawa T, Umezawa Y. Genetically encoded optical probe for detecting release of proteins from mitochondria toward cytosol in living cells and mammals. Anal Chem. 2006;78(23):8076-81.
59. Bacart J, Corbel C, Jockers R, Bach S, Couturier C. The BRET technology and its application to screening assays. Biotechnol J. 2008;3(3):311-24.
60. Pfleger KD, Eidne KA. Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET). Nat Methods. 2006;3(3):165-74.