DISCOVERIES (ISSN 2359-7232), 2016, October-December issue
Submitted: November 30th, 2016; Revised: December 29th, 2016; Accepted: December 29th, 2016; Published: December 31st, 2016;
GO BACK to 2016, October-December issue
GO BACK to DISCOVERIES
A CRISPR View of Biological Mechanisms
Eduardo Martinez, Lilia Sanchez, Neftali Vazquez, Rebecca Marks, Raechel Cedillo, Christa Respondek, Martin Holguin, Michael W. Persans, and Megan Keniry*
Department of Biology, University of Texas Rio Grande Valley, 1201 W. University Dr., Edinburg, TX 78539, USA
*Correspondence to: Megan Keniry, PhD, Department of Biology, University of Texas Rio Grande Valley, 1201 W. University Dr., Edinburg, TX 78539; Phone: 965-665-7463; Fax: 956-665-3657; Email: megan.keniry@utrgv.edu
Abstract
A decade ago, only six manuscripts would be found on a Pubmed search for “CRISPR,” compared to over 2,011 manuscripts in 2016. The purpose of this review is to discuss this emergent technology that has revolutionized molecular biological research in just a few years. Endogenous CRISPR mechanisms are harbored by bacteria and archaea as an adaptive defense system that targets foreign DNA from viruses and plasmids. CRISPR has been adapted as a genome editing tool in a plethora of organisms ranging from yeast to humans. This tool has been employed to create loss of function mutations, gain of function mutations, and tagged alleles in a wide range of settings. CRISPR is now extensively employed for genetic screens. CRISPR has also been adapted to study transcriptional regulation. This versatile and relatively facile technique has, and will be, tremendously impactful in research areas such as biomedical sciences, agriculture, and the basic sciences.
Access full text of the manuscript here: Full text (pdf)
References
1. Jansen, R., Embden, J. D., Gaastra, W., and Schouls, L. M. (2002) Identification of genes that are associated with DNA repeats in prokaryotes, Mol Microbiol 43, 1565-1575
2. Mojica, F.J. and L. Montoliu, On the Origin of CRISPR-Cas Technology: From Prokaryotes to Mammals. Trends Microbiol, 2016. 24(10):811-20.
3. Kleinstiver, B.P., et al., Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature, 2015. 523(7561):481-5.
4. Barrangou, R., et al., CRISPR provides acquired resistance against viruses in prokaryotes. Science, 2007. 315(5819):1709-12.
5. Sorek, R., V. Kunin, andHugenholtz, CRISPR--a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat Rev Microbiol, 2008. 6(3):181-6.
6. Garneau, J.E., et al., The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature, 2010. 468(7320): 67-71.
7. Bikard, D., et al., Programmable repression and activation of bacterial gene expression using an engineered CRISPR-Cas system. Nucleic Acids Res, 2013. 41(15):7429-37.
8. Bosley, K.S., et al., CRISPR germline engineering--the community speaks. Nat Biotechnol, 2015. 33(5):478-86.
9. Cao, J., et al., An easy and efficient inducible CRISPR/Cas9 platform with improved specificity for multiple gene targeting. Nucleic Acids Res, 2016. 44(19): e149.
10. Chen, S., et al., Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell, 2015. 160(6):1246-60.
11. Cong, L., et al., Multiplex genome engineering using CRISPR/Cas systems. Science, 2013. 339(6121):819-23.
12. Feng, Z., et al., Efficient genome editing in plants using a CRISPR/Cas system. Cell Res, 2013. 23(10):1229-32.
13. Gui, T., et al., CRISPR/Cas9-mediated Genome Editing and Mutagenesis of EcChi4 in Exopalaemon carinicauda. G3 (Bethesda), 2016.
14. Hsu, P.D., E.S. Lander, and F. Zhang, Development and applications of CRISPR-Cas9 for genome engineering. Cell, 2014. 157(6):1262-78.
15. Ran, F.A., et al., Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell, 2013. 154(6):1380-9.
16. Ran, F.A., et al., Genome engineering using the CRISPR-Cas9 system. Nat Protoc, 2013. 8(11):2281-308.
17. Shan, Q., et al., Targeted genome modification of crop plants using a CRISPR-Cas system. Nat Biotechnol, 2013. 31(8):686-8.
18. Wang, H., et al., One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell, 2013. 153(4):910-8.
19. Xiao, A., et al., Chromosomal deletions and inversions mediated by TALENs and CRISPR/Cas in zebrafish. Nucleic Acids Res, 2013. 41(14):e141.
20. Yu, Z., et al., Highly efficient genome modifications mediated by CRISPR/Cas9 in Drosophila. Genetics, 2013. 195(1):289-91.
21. Zhang, J. and M.F. White, Hot and crispy: CRISPR-Cas systems in the hyperthermophile Sulfolobus solfataricus. Biochem Soc Trans, 2013. 41(6):1422-6.
22. Zhang, Q., et al., CRISPR-Cas systems target a diverse collection of invasive mobile genetic elements in human microbiomes. Genome Biol, 2013. 14(4):R40.
23. Lo, T.W., et al., Precise and heritable genome editing in evolutionarily diverse nematodes using TALENs and CRISPR/Cas9 to engineer insertions and deletions. Genetics, 2013. 195(2):331-48.
24. Qi, L.S., et al., Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell, 2013. 152(5):1173-83.
25. Doudna, J.A. and E. Charpentier, Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science, 2014. 346(6213):1258096.
26. Friedland, A.E., et al., Heritable genome editing in C. elegans via a CRISPR-Cas9 system. Nat Methods, 2013. 10(8):741-3.
27. Tzur, Y.B., et al., Heritable custom genomic modifications in Caenorhabditis elegans via a CRISPR-Cas9 system. Genetics, 2013. 195(3):1181-5.
28. Mali, P., et al., RNA-guided human genome engineering via Cas9. Science, 2013.339(6121):823-6.
29. Jinek, M., et al., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, 2012. 337(6096):816-21.
30. Hilton, I.B., et al., Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol, 2015. 33(5):510-7.
31. Harrison, M.M., et al., A CRISPR view of development. Genes Dev, 2014. 28(17):1859-72.
32. Laufer, B.I. and S.M. Singh, Strategies for precision modulation of gene expression by epigenome editing: an overview. Epigenetics Chromatin, 2015. 8:34.
33. Ishino, Y., et al., Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol, 1987. 169(12):5429-33.
34. Hermans, P.W., et al., Insertion element IS987 from Mycobacterium bovis BCG is located in a hot-spot integration region for insertion elements in Mycobacterium tuberculosis complex strains. Infect Immun, 1991. 59(8):2695-705.
35. Mojica, F.J., et al., Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol, 2005. 60(2):174-82.
36. Brouns, S.J., et al., Small CRISPR RNAs guide antiviral defense in prokaryotes. Science, 2008. 321(5891):960-4.
37. Marraffini, L.A., CRISPR-Cas immunity in prokaryotes. Nature, 2015. 526(7571):55-61.
38. Marraffini, L.A., The CRISPR-Cas system of Streptococcus pyogenes: function and applications, in Streptococcus pyogenes: Basic Biology to Clinical Manifestations, J.J. Ferretti, D.L. Stevens, and V.A. Fischetti, Editors. 2016: Oklahoma City (OK).
39. Marraffini, L.A. and E.J. Sontheimer, CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science, 2008. 322(5909):1843-5.
40. Marraffini, L.A. and E.J. Sontheimer, Invasive DNA, chopped and in the CRISPR. Structure, 2009. 17(6):786-8.
41. Marraffini, L.A. and E.J. Sontheimer, CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nat Rev Genet, 2010. 11(3):181-90.
42. Deveau, H., J.E. Garneau, and S. Moineau, CRISPR/Cas system and its role in phage-bacteria interactions. Annu Rev Microbiol, 2010. 64:475-93.
43. Barrangou, R., Diversity of CRISPR-Cas immune systems and molecular machines. Genome Biol, 2015. 16:247.
44. Cencic, R., et al., Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage. PLoS One, 2014. 9(10):e109213.
45. Li, M., R. Wang, and H. Xiang, Haloarcula hispanica CRISPR authenticates PAM of a target sequence to prime discriminative adaptation. Nucleic Acids Res, 2014. 42(11):7226-35.
46. Zhang, Y., et al., Comparison of non-canonical PAMs for CRISPR/Cas9-mediated DNA cleavage in human cells. Sci Rep, 2014. 4:5405.
47. Kleinstiver, B.P., et al., Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat Biotechnol, 2015. 33(12):1293-1298.
48. Westra, E.R., et al., Type I-E CRISPR-cas systems discriminate target from non-target DNA through base pairing-independent PAM recognition. PLoS Genet, 2013. 9(9):e1003742.
49. Jiang, Y., et al., Diversity of CRISPR loci and virulence genes in pathogenic Escherichia coli isolates from various sources. Int J Food Microbiol, 2015. 204:41-6.
50. Diez-Villasenor, C., et al., Diversity of CRISPR loci in Escherichia coli. Microbiology, 2010. 156(Pt 5):1351-61.
51. Horvath, P., et al., Diversity, activity, and evolution of CRISPR loci in Streptococcus thermophilus. J Bacteriol, 2008. 190(4):1401-12.
52. Brodt, A., M.N. Lurie-Weinberger, and U. Gophna, CRISPR loci reveal networks of gene exchange in archaea. Biol Direct, 2011. 6(1):65.
53. Makarova, K.S., et al., Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems. Biol Direct, 2011. 6:38.
54. Makarova, K.S., et al., Evolution and classification of the CRISPR-Cas systems. Nat Rev Microbiol, 2011. 9(6):467-77.
55. Rath, D., et al., The CRISPR-Cas immune system: biology, mechanisms and applications. Biochimie, 2015. 117:119-28.
56. Tymensen, L.D., CRISPR1 analysis of naturalized surface water and fecal Escherichia coli suggests common origin. Microbiologyopen, 2016. 5(3):527-33.
57. Fink, G.R., Molecular genetics of yeast: establishing the relationship between a gene and its function. Harvey Lect, 1988. 84:79-96.
58. Finkel, E., Mouse genetics. Australian 'ranch' gears up to mass-produce mutant mice. Science, 2000. 288(5471):1572-3.
59. Whalley, K., Techniques: A CRISPR method of localization. Nat Rev Neurosci, 2016. 17(7):399.
60. Vora, S., et al., Next stop for the CRISPR revolution: RNA-guided epigenetic regulators. FEBS J, 2016. 283(17):3181-93.
61. Vasiliou, S.K., et al., CRISPR-Cas9 System: Opportunities and Concerns. Clin Chem, 2016. 62(10):1304-11.
62. Chiang, T.W., et al., CRISPR-Cas9(D10A) nickase-based genotypic and phenotypic screening to enhance genome editing. Sci Rep, 2016. 6:24356.
63. Wang, F. and L.S. Qi, Applications of CRISPR Genome Engineering in Cell Biology. Trends Cell Biol, 2016. 26(11):875-888.
64. La Russa, M.F. and L.S. Qi, The New State of the Art: Cas9 for Gene Activation and Repression. Mol Cell Biol, 2015. 35(22):3800-9.
65. Perez-Pinera, P., et al., RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods, 2013. 10(10):973-6.
66. Boettcher, M. and M.T. McManus, Choosing the Right Tool for the Job: RNAi, TALEN, or CRISPR. Mol Cell, 2015. 58(4):575-85.
67. Nejepinska, J., M. Flemr, andSvoboda, Control of the interferon response in RNAi experiments. Methods Mol Biol, 2012. 820:133-61.
68. Pebernard, S. and R.D. Iggo, Determinants of interferon-stimulated gene induction by RNAi vectors. Differentiation, 2004. 72(2-3):103-11.
69. Bridge, A.J., et al., Induction of an interferon response by RNAi vectors in mammalian cells. Nat Genet, 2003. 34(3):263-4.
70. Ren, X., et al., Enhanced specificity and efficiency of the CRISPR/Cas9 system with optimized sgRNA parameters in Drosophila. Cell Rep, 2014. 9(3):1151-62.
71. Nemudryi, A.A., et al., TALEN and CRISPR/Cas Genome Editing Systems: Tools of Discovery. Acta Naturae, 2014. 6(3):19-40.
72. Delvecchio, M., et al., Structure of the p300 catalytic core and implications for chromatin targeting and HAT regulation. Nature Structural & Molecular Biology, 2013. 20(9):1040-6.
73. Thakore, P.I., et al., Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements. Nat Methods, 2015. 12(12):1143-9.
74. Xi, L., et al., A novel two-step genome editing strategy with CRISPR-Cas9 provides new insights into telomerase action and TERT gene expression. Genome Biol, 2015. 16:231.
75. Schmidt, J.C., A.J. Zaug, and T.R. Cech, Live Cell Imaging Reveals the Dynamics of Telomerase Recruitment to Telomeres. Cell, 2016. 166(5):1188-1197 e9.
76. Zhong, F.L., et al., TPP1 OB-Fold Domain Controls Telomere Maintenance by Recruiting Telomerase to Chromosome Ends. Cell, 2012. 150(3):481-494.
77. Nelles, D.A., et al., Programmable RNA Tracking in Live Cells with CRISPR/Cas9. Cell, 2016. 165(2):488-96.
78. Meda, P., Probing the function of connexin channels in primary tissues. Methods, 2000. 20(2):232-44.
79. Thiel, W.H. and P.H. Giangrande, AFBI assay - Aptamer Fluorescence Binding and Internalization assay for cultured adherent cells. Methods, 2016. 103:180-7.
80. McKeague, M. and M.C. Derosa, Challenges and opportunities for small molecule aptamer development. J Nucleic Acids, 2012. 2012:748913.
81. Clarke, J.D. and C. Tickle, Fate maps old and new. Nat Cell Biol, 1999. 1(4):E103-9.
82. Lu, R., et al., Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding. Nat Biotechnol, 2011. 29(10):928-33.
83. McKenna, A., et al., Whole-organism lineage tracing by combinatorial and cumulative genome editing. Science, 2016. 353(6298):aaf7907.
84. Wang, T., et al., Genetic screens in human cells using the CRISPR-Cas9 system. Science, 2014. 343(6166):80-4.
85. Shalem, O., et al., Genome-scale CRISPR-Cas9 knockout screening in human cells. Science, 2014. 343(6166):84-7.
86. Shalem, O., N.E. Sanjana, and F. Zhang, High-throughput functional genomics using CRISPR-Cas9. Nat Rev Genet, 2015. 16(5):299-311.
87. Bassett, A.R., L. Kong, and J.L. Liu, A genome-wide CRISPR library for high-throughput genetic screening in Drosophila cells. J Genet Genomics, 2015. 42(6):301-9.
88. Kiessling, M.K., et al., Identification of oncogenic driver mutations by genome-wide CRISPR-Cas9 dropout screening. BMC Genomics, 2016. 17(1):723.
89. Cross, B.C., et al., Increasing the performance of pooled CRISPR-Cas9 drop-out screening. Sci Rep, 2016. 6:31782.
90. Sanjana, N.E., Genome-scale CRISPR pooled screens. Anal Biochem, 2016.
91. Sanjana, N.E., O. Shalem, and F. Zhang, Improved vectors and genome-wide libraries for CRISPR screening. Nat Methods, 2014. 11(8):783-4.
92. Ruiz, S., et al., A Genome-wide CRISPR Screen Identifies CDC25A as a Determinant of Sensitivity to ATR Inhibitors. Mol Cell, 2016. 62(2):307-13.
93. Kim, H.J., et al., Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells. Int J Cancer, 2017. 140(1):109-119.
94. Kwok, M., et al., ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells. Blood, 2016. 127(5):582-95.
95. Zheng, X.F. and J.V. Ruderman, Functional analysis of the P box, a domain in cyclin B required for the activation of Cdc25. Cell, 1993. 75(1):155-64.
96. Perry, J.A. and S. Kornbluth, Cdc25 and Wee1: analogous opposites? Cell Div, 2007. 2:12.
97. Recent patents in CRISPR technology. Nat Biotechnol, 2016. 34(5):511.
98. CRISPR patents to go on trial. Nat Biotechnol, 2016. 34(2):121.
99. Egelie, K.J., et al., The emerging patent landscape of CRISPR-Cas gene editing technology. Nat Biotechnol, 2016. 34(10):1025-1031.
100. Fan, X., G. Liao, and J. Xie, Intellectual property education exemplified by the patents on the CRISPR/Cas9 system. Yi Chuan, 2014. 36(12):1269-73.
101. Grushkin, D., DuPont in CRISPR-Cas patent land grab. Nat Biotechnol, 2016. 34(1):13.
102. Ledford, H., Titanic clash over CRISPR patents turns ugly. Nature, 2016. 537(7621):460-1.
103. Ledford, H., How the US CRISPR patent probe will play out. Nature, 2016. 531(7593):149.
104. Ledford, H., Bitter fight over CRISPR patent heats up. Nature, 2016. 529(7586):265.
105. Peng, Y., The morality and ethics governing CRISPR-Cas9 patents in China. Nat Biotechnol, 2016. 34(6):616-8.
106. Sheridan, C., First CRISPR-Cas patent opens race to stake out intellectual property. Nat Biotechnol, 2014. 32(7):599-601.
107. Sherkow, J.S., Law, history and lessons in the CRISPR patent conflict. Nat Biotechnol, 2015. 33(3):256-7.
108. Bellver Capella, V., [Crispr-Cas9 Gene Editing Revolution and the Its Ethical and Legal Challenges]. Cuad Bioet, 2016. 27(90):223-39.
109. Caplan, A.L., et al., No time to waste--the ethical challenges created by CRISPR: CRISPR/Cas, being an efficient, simple, and cheap technology to edit the genome of any organism, raises many ethical and regulatory issues beyond the use to manipulate human germ line cells. EMBO Rep, 2015. 16(11):1421-6.
110. Fogleman, S., et al., CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations. Am J Stem Cells, 2016. 5(2):39-52.
111. Hawkes, N., New gene editing technique CRISPR-Cas9 raises important ethical questions, says advisory body. BMJ, 2016. 354:i5318.
112. Ledford, H., UK bioethicists eye designer babies and CRISPR cows. Nature, 2016. 538(7623):17.
113. Perkel, J., CRISPR/Cas faces the bioethics spotlight. Biotechniques, 2015. 58(5):223-7.
114. Liang, P., et al., CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell, 2015. 6(5):363-72.
115. Su, S., et al., CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. Sci Rep, 2016. 6:20070.
116. Li, Q., et al., Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor. Oncotarget, 2016.
117. Yang, Y., L. Ding, Wang, Dramatic response to anti-PD-1 therapy in a patient of squamous cell carcinoma of thymus with multiple lung metastases. J Thorac Dis, 2016. 8(7):E535-7.
118. Lin, Z., et al., PD-1 Antibody Monotherapy for Malignant Melanoma: A Systematic Review and Meta-Analysis. PLoS One, 2016. 11(8):e0160485.
119. Galloway, S.J. and A.L. Harwood-Nuss, Sickle-cell anemia--a review. J Emerg Med, 1988. 6(3):213-26.
120. da Fonseca, M., H.S. Oueis, and P.S. Casamassimo, Sickle cell anemia: a review for the pediatric dentist. Pediatr Dent, 2007. 29(2):159-69.
121. Dever, D.P., et al., CRISPR/Cas9 beta-globin gene targeting in human haematopoietic stem cells. Nature, 2016. 539(7629):384-389.
122. Kim, J. and J.S. Kim, Bypassing GMO regulations with CRISPR gene editing. Nat Biotechnol, 2016. 34(10):1014-1015.
123. Shan, Q., et al., Genome editing in rice and wheat using the CRISPR/Cas system. Nat Protoc, 2014. 9(10):2395-410.
124. Hai, T., et al., One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res, 2014. 24(3):372-5.
125. Honda, T. and K. Tomonaga, Endogenous non-retroviral RNA virus elements evidence a novel type of antiviral immunity. Mob Genet Elements, 2016. 6(3):e1165785.
News & Events Latest news from Discoveries
- 2022, April| AWARDS!
2022 Discoveries Award winning articles!
- Kinal Bhatt et al. 2021 (Larking Health System, FL, USA); Bhatt K, Agolli A, Patel MH, et al. High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections. Discoveries. 2021;9(1):e126.
27 citations in the past 1 year - $1000 prize- Hasnain Jan et al. 2020 (Quaid-i-Azam University, Pakistan); Jan H, Faisal S, Khan A, et al. COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus. Discoveries. 2020;8(2):e108.
23 citations in the past 2 years - $400 prizeCongratulations! Prizes will be received by the awardees in July 2022!
- 2021, July| 2021, Jul-September
Due to the high volume of the submitted articles, both Discoveries and Discoveries Reports are experiencing processing and publication delays during the months of July-September 2021. We will get back to the normal processing and publication times starting in October 2021. Note that our editorial and administrativ work is fully funded by our publishing house at this time and we are striving to KEEP THE NO FEE/NO CHARGE strategy in place as long as possible.
- 2021, January| AWARDS!
2022 DISCOVERIES AWARDS! Discoveries will offer $1000 and $400 awards in early 2022, for the most cited (2021 ISI Citations) and visible articles published in 2018-2021.
- 2020, November| Follow us on Twitter!
You can now follow the latest Discoveries news and updates on Twitter! (@DiscoveriesNews)
- 2020, August| For Authors!
Due to a high volume of article submissions, our peer-review process takes more than usual. The pre-screening decision is released in 1-2 days, while the peer-review process lasts between 10 and 20 days.
- 2020, April | For Authors!
WE DO NOT TOLERATE ANY MISCONDUCT! Please be aware that we are testing all received articles with specialized software for PLAGIARISM and WE WILL TAKE MEASURES if your article is already published or in consideration for publication by other journals! This may result in serious professional consequences for the authors. The latest striking case is the following article which is already published and was re-submitted here.
- 2020, April | For Authors!
We are happy to let you know that all articles published in Discoveries are now included in PubMedCentral (PMC). New accepted articles will be included in PMC and PubMed within 1-2 weeks after their publication.
- 2020, January | For Authors!
Starting in January 2020, Discoveries will also consider articles submitted by Discoveries' Editorial Board members. However, only a small number of such articles (maximum 4 articles/year) will be considered for publication after the peer-review process, and the authors who are also our editors will be clearly disclosed on our website.
- 2019, September | Indexed by PMC
Discoveries is now indexed by PubMedCentral and Pubmed. The agreement with US National Library of Medicine was signed on September 10, 2019. Our next step is ISI Web of Science indexing. NOTE: previously published articles will be included on PubMed in early 2020.
- 2019, September | PubMed inclusion!
We are happy to let you know that Discoveries successfuly passed the last step (Technical Review) required for PubMedCentral and PubMed inclusion!
- 2019, July | PubMed inclusion News!
We are happy to receive positive comments from PMC/NLM-NIH regarding Discoveries' last step (Technical Review) required for PubMedCentral and PubMed inclusion. We will let you know once whole indexing process is completed.
- 2019| Sharing and Distribution!
All articles published in Discoveries are Open Access articles distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited and it is not used for commercial purposes.
- 2018-2019 | For Authors!
From now on and for at least 1 year, we will only accept articles from authors that are NOT members of Discoveries' Editorial Board. All articles submitted by our editors will be immediately rejected until further notice (one accepted article was already rejected).
- 2018 | PubMed inclusion News!
Discoveries successfully passed the Scientific Quality Review by NLM-NIH for PubMedCentral and PubMed indexing. This is the first and the most important step towards PubMedCentral and PubMed indexing! The second (last) step is the Technical Review.
- 2016, April | Faster Peer-Review
Starting on April 13th 2016, all articles selected for a peer-review will receive the post peer-review decision within ~10 days. The initial pre-screening time will remain the same (48h from the submission of the manuscript). This decision will significantly accelerate the publication, with no effect on the quality of the peer-review process.
- 2016, February | Manuscript submission
Discoveries is commited to excellence, quality and high editorial standards. We are receiving an increasing number of manuscripts for which the identity of the authors/corresponding author can't be verified. Please NOTE that ALL these articles were and will be immediately REJECTED. Indicating an institutional email address is the easiest way to overcome this problem! Moreover, we do not accept any pressure on our editorial board to accept a manuscript. This results in a prompt rejection of the article.
Editorial Policies - 2016, January | Main Objective
After reaching all proposed milestones until now (including being indexed by Google Scholar in 2014), Discoveries' next Aim is PubMed indexing of all its articles (already published and upcoming). There will be no charge for the submission or publication of articles before Discoveries is indexed.
- 2015, August | Discoveries - on PubMed
We are happy to announce that our first Discoveries articles were included in PMC and PubMed. More articles (submitted by NIH funded authors) are now processed for being included.
Discoveries articles now on PubMed - 2015, April | Special Issue
DISCOVERIES published the SPECIAL ISSUE entitled "INFLAMMATION BETWEEN DEFENSE AND DISEASE: Impact on Tissue Repair and Chronic Sickness".
Special Issue on "Inflammation" - 2015 | Ischemia Collection
DISCOVERIES launched a call for papers for a Collection of Articles with focus on "ISCHEMIA". If you are interested to submit a manuscript, please contact us at info@discoveriesjournals.org
- 2014, September | Special Issue
DISCOVERIES just publish the SPECIAL ISSUE entitled "CELL SECRETION & MEMBRANE FUSION" in September 2014. Initially scheduled for publication between October 2014-March 2015, this issue was successfully published earlier than scheduled.
Special Issue - 2014, April | Indexed by Google Scholar
All our published articles are now indexed by Google Scholar! First citations to Discoveries articles are included! Search for the article's title (recommended) or the authors:
Google Scholar Search - 2014 | DISCOVERIES
DOIs (Digital Object Identifiers) are now assigned to all our published manuscripts in Discoveries. DOI uniquely identifies an article and is provided by CrossRef.
CrossRef - 2013, July | Manuscript Submission
Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)! There are NO fees for the manuscript submission or publishing of the accepted manuscripts.
read more - 2013, July | DISCOVERIES
We are now ACCEPTING MANUSCRIPTS for publishing in DISCOVERIES. We aim publishing a small number of high impact experimental articles & reviews (around 40/year) to maintain a high impact factor. Domains of interest: all areas related to Medicine, Biology and Chemistry ...
read more