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Gene Therapy

  1. Dias MM, Vidigal J, Sequeira DP, Alves PM, Teixeira AP, Roldão A. 2021. Insect High FiveTM cell line development using site-specific flipase recombination technology. G3 Genes|Genomes|Genetics. doi: 10.1093/g3journal/jkab166

  2. Fernandes B, Correia R, Sousa M, Carrondo MJT, Roldão A. 2021. Integrating high cell density cultures with adapted laboratory evolution for improved Gag-HA virus-like particles production in stable insect cell lines. Biotechnology and Bioengineering. doi: 10.1002/bit.27766

  3. Correia R, Fernandes B, Alves PM, Carrondo MJT, Roldao A. 2020. Improving Influenza HA-Vlps Production in Insect High Five Cells via Adaptive Laboratory Evolution. Vaccines. 8(4), 589. doi:10.3390/vaccines8040589

  4. Guerreiro MR, Fernandes AR, Coroadinha AS. 2020. Evaluation of Structurally Distorted Split GFP Fluorescent Sensors for Cell-Based Detection of Viral Proteolytic Activity. Sensors. 21(1), 24. doi:10.3390/s21010024

  5. Moreira AS, Cavaco D, Faria T, Alves PM, Carrondo MJT, Peixoto C. 2020. Advances in  Lentivirus Purification. Biotechnology Journal. doi:10.1002/biot.202000019

  6. Pais DAM, Brown C, Neuman A, Mathur K, Isidro IA, Alves PM, Slade PG. 2020. Dielectric spectroscopy to improve the production of rAAV used in Gene Therapy. Processes. 8(11):1456. doi:10.3390/pr8111456

  7. Rodrigues AF, Fernandes P, Laske T, Castro R, Alves PM, Genzel Y, Coroadinha AS. 2020. Cell Bank Origin of MDCK Parental Cells Shapes Adaptation to Serum-Free Suspension Culture and Canine Adenoviral Vector Production. International Journal of Molecular Sciences. 21(17):6111. doi:10.3390/ijms21176111

  8. Ferreira MV, Cabral ET, Coroadinha AS. 2020. Progress and Perspectives in the Development of Lentiviral Vector Producer Cells. Biotechnology Journal. 2000017. doi:10.1002/biot.202000017

  9. Formas-Oliveira AS, Basílio JS, Rodrigues AF, Coroadinha AS. 2020. Overexpression of ER Protein Processing and Apoptosis Regulator Genes in Human Embryonic Kidney 293 Cells Improves Gene Therapy Vectors Production. Biotechnology Journal. 1900562. doi:10.1002/biot.201900562 

  10. Pais DA, Galrão PR, Kryzhanska A, Barbau J, Isidro IA, Alves PM. 2020. Holographic Imaging of Insect Cell Cultures: Online Non-Invasive Monitoring of Adeno-Associated Virus Production and Cell Concentration. Processes 8(4): 487. doi:10.3390/pr8040487 

  11. Moreira AS, Silva AC, Sousa MFQ, Hagner-McWhirterc A, Ahlénc G, Lundgren M, Coroadinha AS, Alves PM, Peixoto C, Carrondo MJT. 2020. Establishing Suspension Cell Cultures for Improved Manufacturing of Oncolytic Adenovirus. Biotechnol J. doi:10.1002/biot.201900411

  12. Tomás HA, Mestre DA, Rodrigues AF, Guerreiro MR, Carrondo MJT, Coroadinha AS. 2019. Improved GaLV-TR Glycoproteins to Pseudotype Lentiviral Vectors: Impact of Viral Protease Activity in the Production of LV Pseudotypes. Mol Ther Methods Clin Dev. 15:1-8. doi:10.1016/j.omtm.2019.08.001

  13. Pais DAM, Portela RMC, Carrondo MJT, Isidro IA, Alves PM. 2019. Enabling PAT in insect cell bioprocesses: In situ monitoring of recombinant adeno-associated virus production by fluorescence spectroscopy. Biotechnol Bioeng. Jul 17 https://doi.org/10.1002/bit.27117

  14. Pinto C, Silva G, Ribeiro AS, Oliveira M, Garrido M, Bandeira VS, Nascimento A, Coroadinha AS, Peixoto C, Barbas A, Paredes J, Brito C, Alves PM. 2019. Evaluation of AAV-mediated delivery of shRNA to target basal-like breast cancer genetic vulnerabilities. J Biotechnol. Jul 20;300:70-77. https://doi.org/10.1016/j.jbiotec.2019.05.016

  15. Guerreiro MR, Freitas DF, Alves PM, Coroadinha AS. 2019. Detection and Quantification of Label-Free Infectious Adenovirus Using a Switch-On Cell-Based Fluorescent Biosensor. ACS Sens. Jun 28;4(6):1654-1661. https://doi.org/10.1021/acssensors.9b00489

  16. Schmolka N, Papotto PH, Romero PV, et al. 2018. MicroRNA-146a controls functional plasticity in gammadelta T cells by targeting NOD1. Sci Immunol. 3(23):eaao1392. https://doi.org/10.1126/sciimmunol.aao1392​

  17. Tomás HA, Rodrigues AF, Carrondo MJT, Coroadinha AS. 2018. LentiPro26: Novel stable cell lines for constitutive lentiviral vector production. Sci Rep. 8(5271). https://doi.org/10.1038/s41598-018-23593-y.​

  18. Bandeira VS, Tomas HA, Alice E, Carrondo MJT, Coroadinha AS. 2017. Disclosing the Parameters Leading to High Productivity of Retroviral Producer Cells Lines: Evaluating Random Versus Targeted Integration. HUMAN GENE THERAPY METHODS. 28, 78-90.  http://dx.doi.org/10.1089/hgtb.2016.149

  19. Soares HR, Castro R, Tomas HA, Rodrigues AF, Gomes-Alves P, Bellier B, Klatzmann D, Carrondo MJ, Alves PM, Coroadinha AS. 2016. Tetraspanins displayed in retrovirus-derived virus-like particles and their immunogenicity. Vaccine. http://dx.doi.org/10.1016/j.vaccine.2015.12.015

  20. Fernandes CS, Castro R, Coroadinha AS, Roque AC. 2016. Small synthetic ligands for the enrichment of viral particles pseudotyped with amphotropic murine leukemia virus envelope. J Chromatogr A. pii: S0021-9673(16)30125-X. http://dx.doi.org/10.1016/j.chroma.2016.02.026

  21. Silva AC, Teixeira AP, Alves PM. 2016. Impact of Adenovirus infection in host cell metabolism evaluated by 1H NMR spectroscopy. J Biotechnol. http://dx.doi.org/10.1016/j.jbiotec.2016.05.025

  22. Fernandes CS, Castro R, Coroadinha AS, Roque AC. 2016. Small synthetic ligands for the enrichment of viral particles pseudotyped with amphotropic murine leukemia virus envelope. J Chromatogr A. pii: S0021-9673(16)30125-X. http://dx.doi.org/10.1016/j.chroma.2016.02.026

  23. Simão D, Pinto C, Fernandes P, Peddie CJ, Piersanti S, Collinson LM, Salinas S, Saggio I, Schiavo G, Kremer EJ, Brito C, Alves PM. 2016. Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model. Gene Ther. http://dx.doi.org/10.1038/gt.2015.75

  24. Rodrigues A F, Guerreiro M R, Formas-Oliveira A S, Fernandes P, Blechert A-K, Genzel Y, Alves P M, Hu W S, Coroadinha AS. 2015. Increased titer and reduced lactate accumulation in recombinant retrovirus production through the down-regulation of HIF1 and PDK. Biotechnology and Bioengineering Jul 1. http://dx.doi.org/10.1002/bit.25691.

  25. Rodrigues AF, Soares HR, Guerreiro MR, Alves PM, Coroadinha AS. 2015. Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology. Biotechnol J. Sep;10(9):1329-44. http://dx.doi.org/10.1002/biot.201400387.

  26. Rodrigues AF, Formas-Oliveira AS, Guerreiro M, Tomas H, Alves PM and Coroadinha AS. 2015. Single step cloning-screening method: a new tool for developing and studying high titer viral vector producer cells. Gene Ther, May 4. http://dx.doi.org/10.1038/gt.2015.44

  27. Castro R, Fernandes P, Laske T, Sousa MFQ, Genzel Y, Scharfenberg K, Alves PM, Coroadinha AS. 2015. Production of canine adenovirus type 2 in serum-free suspension cultures of MDCK cells. Appl Microbiol Biotechnol http://dx.doi.org/10.1007/s00253-015-6636-8

  28. Nestola P, Peixoto C, Silva RJS, Alves PM, Mota JPB, Carrondo MJT 2015. Improved virus purification processes for vaccines and gene therapy. Biotechnology and Bioengineering, 112(5):843-57. http://dx.doi.org/10.1002/bit.25545

  29. Fernandes P, Simão D, Guerreiro MR, Kremer EJ, Coroadinha AS, Alves PM. 2015. Impact of adenovirus life cycle progression on the generation of canine helper-dependent vectors. Gene Ther. Jan;22(1):40-9. http://dx.doi.org/10.1038/gt.2014.92

  30. Fernandes P, Almeida AI, Kremer EJ, Alves PM, Coroadinha AS. 2015. Canine helper-dependent vectors production: implications of Cre activity and co-infection on adenovirus propagation. Sci Rep. Mar 16;5:9135. http://dx.doi.org/10.1038/srep09135

  31. Nestola P, Silva RJS, Peixoto C, Alves PM, Carrondo MJT, Mota JPB 2015. Robust design of adenovirus purification by two-column, simulated countercurrent, size-exclusion chromatography. Journal of Biotechnology; http://dx.doi.org/10.1016/j.jbiotec.2015.01.030

  32. Fernandes P, Simão D, Guerreiro MR, Kremer EJ, Coroadinha AS, Alves PM. 2015. Impact of adenovirus life cycle on the generation of canine helper-dependent vectors. Gen Ther 22, 40-49. http://dx.doi.org/10.1038/gt.2014.92  

  33. Rodrigues AF, Carrondo MJ, Alves PM, Coroadinha AS, 2014. Cellular targets for improved manufacturing of virus-based biopharmaceuticals in animal cells. Trends in Biotechnology Dec;32(12):602-7. http://dx.doi.org/10.1016/j.tibtech.2014.09.010

  34. Nestola P, Villain L, Peixoto C, Martins DL, Alves PM, Carrondo MJT, Mota JPB, 2014.

  35. Impact of grafting on the design of new membrane adsorbers for adenovirus purification.

  36. Journal of Biotechnology, 181: 1–11. http://dx.doi.org/10.1016/j.jbiotec.2014.04.003

  37. Nestola P, Silva RJS, Peixoto C, Alves PM, Carrondo MJT, Mota JPB. 2014. Adenovirus purification by two-column, size-exclusion, simulated countercurrent chromatography. Journal of Chromatography A,1347: 111–121. http://dx.doi.org/10.1016/j.chroma.2014.04.079  

  38. Rodrigues AF, Formas-Oliveira AS, Bandeira, VS, Alves PM, Hu WS, Coroadinha AS. 2013. Metabolic pathways recruited in the production of a recombinant enveloped virus: mining targets for process and cell engineering. Metab. Eng., 20, 131-137. http://dx.doi.org/10.1016/j.ymben.2013.10.001

  39. Fernandes P, Peixoto C, Santiago VM, Kremer EJ, Coroadinha AS, Alves PM, 2013. Bioprocess development for canine adenovirus type 2 vectors. Gene Ther. Apr;20(4):353-60. http://dx.doi.org/10.1038/gt.2012.52

  40. Fernandes P, Santiago VM, Rodrigues AF, Tomás H, Kremer EJ, Alves PM, Coroadinha AS. 2013. Impact of E1 and Cre on Adenovirus Vector Amplification: Developing MDCK CAV-2-E1 and E1-Cre Transcomplementing Cell Lines. PLoS One.8(4):e60342. http://dx.doi.org/10.1371/journal.pone.0060342

  41. Rodrigues AF, Amaral AI, Veríssimo V, Alves PM, Coroadinha AS, 2012. Adaptation of retrovirus producer cells to serum deprivation: Implications in lipid biosynthesis and vector production. Biotechnol Bioeng, 109 (5): 1269-79. http://dx.doi.org/10.1002/bit.24410

  42. Carrondo MJ, Panet A, Wirth D, Coroadinha AS, Cruz P, Falk H, Schucht R, Dupont F, Geny-Fiamma C, Merten OW, Hauser H, 2011. Integrated strategy for the production of therapeutic retroviral vectors. Hum Gene Ther, 22(3): 370-79. http://dx.doi.org/10.1089/hum.2009.165

  43. Gama-Norton L, Botezatu L, Herrmann S, Schweizer M, Alves PM, Hauser H, Wirth D, 2011. Lentivirus production is influenced by SV40 large T-antigen and chromosomal integration of the vector in HEK293 cells. Hum Gene Ther, 22(10):1269-79. http://dx.doi.org/10.1089/hum.2010.143

  44. Real G, Monteiro F, Burger C, Alves PM, 2011. Improvement of lentiviral transfer vectors using cis-acting regulatory elements for increased gene expression. Appl Microbiol Biotechnol, 91:1581-91. http://dx.doi.org/10.1007/s00253-011-3392-2

  45. Cruz PE, Rodrigues T, Carmo M, Wirth D, Amaral AI, Alves PM, Coroadinha AS, 2011. Manufacturing of retroviruses. Methods Mol Biol, 737:157-82. http://dx.doi.org/10.1007/978-1-61779-095-9_7

  46. Silva AC, Peixoto C, Lucas T, Kuppers C, Cruz PE, Alves PM, Kochanek S, 2010. Adenovirus vector production and purification. Curr Gene Ther, 10(6):437-55.

  47. Coroadinha AS, Gama-Norton L, Amaral AI, Hauser H, Alves PM, Cruz PE, 2010. Production of retroviral vectors. Curr Gene Ther, 10(6):456-73.

  48. Bernal V, Carinhas N, Yokomizo A, Carrondo MJ, Alves PM, 2009. Cell density effect in the Baculovirus-Insect cells system: a quantitative analysis of energetic metabolism. Biotechnol Bioeng, 104(1):162-80. http://dx.doi.org/10.1002/bit.22364

  49. Carinhas N, Bernal V, Yokomizo AY, Carrondo MJ, Oliveira R, Alves PM, 2009. Baculovirus production for gene therapy: the role of cell density, multiplicity of infection and medium exchange. Appl Microbiol Biotechnol, 81(6):1041-49. http://dx.doi.org/10.1007/s00253-008-1727-4

  50. Rodrigues AF, Carmo M, Alves PM, Coroadinha AS, 2009. Retroviral vector production under serum deprivation: the role of lipids. Biotechnol Bioeng, 104(6):1171-81. http://dx.doi.org/10.1002/bit.22499

  51. Vicente T, Peixoto C, Carrondo MJ, Alves PM, 2009. Virus production for clinical gene therapy. Methods Mol Biol, 542:447-70. http://dx.doi.org/10.1007/978-1-59745-561-9_24

  52. Vicente T, Peixoto C, Carrondo MJ, Alves PM, 2009. Purification of recombinant baculoviruses for gene therapy using membrane processes. Gene Ther, 16:766-775. http://dx.doi.org/10.1038/gt.2009.33

  53. Carmo M, Alves A, Rodrigues AF, Coroadinha AS, Carrondo MJ, Alves PM, Cruz PE, 2009 Stabilization of gammaretroviral and lentiviral vectors: from production to gene transfer. J Gene Med, 11:670-78. http://dx.doi.org/10.1002/jgm.1353

  54. Ferreira TB, Perdigão R, Silva AC, Zhang C, Aunins JG, Carrondo MJ, Alves PM, 2009. 293 cell cycle synchronisation in adenovirus vector production. Biotechnol Prog, 25(1):235-43. http://dx.doi.org/10.1002/btpr.64

  55. Carmo M, Dias JD, Panet A, Coroadinha AS, Carrondo MJ, Alves PM, Cruz PE, 2009. Thermosensitivity of the reverse transcription process as an inactivation mechanism of lentiviral vectors. Hum Gene Ther, 20(10):1168-76. http://dx.doi.org/10.1089/hum.2009.068

  56. Amaral AI, Coroadinha AS, Merten O-W, Alves PM, 2008. Improving retroviral vectors production: role of carbon sources in lipid biosynthesis. J Biotechnol, 138: 57-66. http://dx.doi.org/10.1016/j.jbiotec.2008.08.005

  57. Carmo M, Panet A, Carrondo MJ, Alves PM, Cruz PE, 2008. From retroviral vector production to gene transfer: spontaneous inactivation is caused by loss of reverse transcription capacity. J Gene Med, 10:383-91. http://dx.doi.org/10.1002/jgm.1163

  58. Rodrigues T, Alves A, Lopes A, Carrondo MJ, Alves PM, Cruz PE, 2008. Removal of envelope protein-free retroviral vectors by anion exchange chromatography to improve product quality. J Sep Sci, 31:3509-18. http://dx.doi.org/10.1002/jssc.200800195

  59. Carrondo MJ, Merten OW, Haury M, Alves PM, Coroadinha AS, 2008. Impact of retroviral vector components stoichiometry on packaging cell lines: effects on productivity and vector quality. Hum Gene Ther, 19:199-210. http://dx.doi.org/doi:10.1089/hum.2007.0101

  60. Ferreira TB, Carrondo MJ, Alves PM, 2007. Effect of ammonia production on intracellular pH consequent effect on adenovirus vector production. J Biotechnol, 129(3):433-38. http://dx.doi.org/10.1016/j.jbiotec.2007.01.010

  61. Rodrigues T, Carvalho A, Carmo M, Carrondo MJ, Alves PM, Cruz PE, 2007. Scaleable purification process for gene therapy retroviral vectors. J Gene Med, 9(4):233-43. http://dx.doi.org/10.1002/jgm.1021

  62. Rodrigues T, Carrondo MJ, Alves PM, Cruz PE, 2007. Purification of retroviral vectors for clinical application: biological implication and technological challenges. J Biotechnol, 127:520-41. http://dx.doi.org/10.1016/j.jbiotec.2006.07.028

  63. Wirth D, Gama-Norton L, Riemer P, Sandhu U, Schucht R, Hauser H, 2007. Road to precision: recombinase-based targeting technologies for genome engineering. Curr Opin Biotechnol, 18:411–19. http://dx.doi.org/10.1016/j.copbio.2007.07.013

  64. Coroadinha AS, Silva AC, Pires E, Coelho A, Alves PM, Carrondo MJ, 2006. Effect of osmotic pressure on the production of retroviral vectors: enhancement in vector stability. Biotechnol Bioeng, 94(2):322-9. http://dx.doi.org/10.1002/bit.20847

  65. Rodrigues T, Carvalho A, Roldao A, Carrondo MJ, Alves PM, Cruz PE, 2006. Screening anion-exchange chromatographic matrices for isolation of onco-retroviral vectors. J Chromatogr B, 837(1-2):59-68. http://dx.doi.org/10.1016/j.jchromb.2006.03.061

  66. Schucht R, Coroadinha AS, Zanta-Boussif MA, Verhoeyen E, Carrondo MJ, Hauser H, Wirth D, 2006. A new generation of retroviral producer cells: predictable and stable virus production by Flp-mediated site-specific integration of retroviral vectors. Mol Ther, 14(2):285-92. http://dx.doi.org/10.1016/j.ymthe.2005.12.003

  67. Carmo M, Faria TQ, Falk H, Coroadinha AS, Teixeira M, Merten OW, Geny-Fiamma C, Alves PM, Danos O, Panet A, Carrondo MJ, Cruz PE, 2006. Relationship between retroviral vector membrane and vector stability. J Gen Virol, 87(5):1349-56. http://dx.doi.org/10.1099/vir.0.81302-0

  68. Cruz PE, Silva AC, Roldao A, Carmo M, Carrondo MJ, Alves PM, 2006.Screening of novel excipients for improving the stability of retroviral and adenoviral vectors. Biotechnol Prog, 22(2):568-76. http://dx.doi.org/10.1021/bp050294y

  69. Coroadinha AS, Ribeiro J, Roldão A, Cruz PE, Alves PM, Merten O-W, Carrondo MJ, 2006. Effect of medium sugar source on the production of retroviral vectors for gene therapy. Biotechnol Bioeng, 94(1):24-36. http://dx.doi.org/10.1002/bit.20778

  70. Coroadinha AS, Alves PM, Santos SS, Cruz PE, Merten, OW, Carrondo MJ, 2006. Retrovirus producer cell line metabolism: implications on viral productivity. Appl Microbiol Biotechnol. 72(6):1125-35. http://dx.doi.org/10.1007/s00253-006-0401-y

  71. Coroadinha AS, Schucht R, Gama-Norton L, Wirth D, Hauser H, Carrondo MJ, 2006. The use of recombinase mediated cassette exchange in retroviral vector producer cell lines: predictability and efficiency by transgene exchange. J Biotechnol, 124(2):457-68. http://dx.doi.org/10.1016/j.jbiotec.2006.01.037

  72. Ferreira TB, Alves PM, Aunins JG, Carrondo MJ, 2005. Use of adenoviral vectors as veterinary vaccines. Gene Ther, 12(S1):73-83. http://dx.doi.org/10.1038/sj.gt.3302618

  73. Carmo M,  Peixoto CC, Coroadinha AS, Alves PM, Cruz PE, Carrondo MJ, 2004. Quantitation of MLV-based retroviral vectors using real-time RT-PCR. J Virol Methods, 119:115-9. http://dx.doi.org/10.1016/j.jviromet.2004.03.007

  74. Cruz PE, L Maranga, MJ Carrondo, 2002. Integrated process optimization: lessons from retrovirus and virus-like particle production. J Biotechnol, 99:199-214. http://dx.doi.org/10.1016/S0168-1656(02)00210-9

  75. Merten OW, Cruz PE, Rochette C, Geny-Fiamma C, Bouquet C, Goncalves D, Danos O, Carrondo MJ, 2001. Comparison of different bioreactor systems for the production of high titer retroviral vectors. Biotechnol Prog, 17:326-35. http://dx.doi.org/10.1021/bp000162z

  76. Morais VA, Serpa J, Palma AS, Costa T, Maranga L, Costa J, Wu N, Ataai MM, 2001. Expression and characterization of recombinant human alpha-3/4-fucosyltransferase III from Spodoptera frugiperda (Sf9) and Trichoplusia ni (Tn) cells using the baculovirus expression system. Biochem J, 353:719-25. http://www.biochemj.org/bj/353/bj3530719.htm

  77. Cruz PE, Almeida JS, Murphy PN, Moreira JL, Carrondo MJ, 2000. Modeling retrovirus production for gene therapy. 1. Determination of optimal bioreaction mode and harvest strategy. Biotechnol Prog, 16:213-21. http://dx.doi.org/10.1021/bp9901466

  78. Cruz PE, Goncalves D, Almeida J, Moreira JL, Carrondo MJ, 2000. Modeling retrovirus production for gene therapy. 2. Integrated optimization of bioreaction and downstream processing. Biotechnol Prog, 16:350-57. http://dx.doi.org/10.1021/bp000017l

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