Role of Biomolecules and Biologics in Precision Medicine, Personalized Medicine, and Emerging Therapies

GUEST EDITORIAL
Gundu H. R. Rao

 
International Journal of Biomedicine. 2022;12(1):70-81.
DOI: 10.21103/Article12(1)_GE
Originally published March 10, 2022

Abstract: 

In the 1990s, DNA sequencing technologies could only read bite-sized pieces of DNA. Then came the human genome project (HGP),  a thirteen-year international effort, 1990-2003, with the primary goal of discovering the complete set of human genes, sequencing nucleotides, and making the information accessible worldwide for further biological studies. We have come a long way since that time in terms of sequencing the genes of the human genome. Now the researchers can sequence the DNA and analyze gene-expressed proteins in individual cells, allowing them to dissect the complexities of genetic diseases with exceptional details. Currently, technologies are available for single-cell or multi-omics platforms to analyze genotype and phenotype. The completion of this one-of-a-kind project created public expectations for immediate, better health care delivery and possible cures for 'so called' incurable diseases. The HGP was the single most influential investment made in modern basic science research. A monumental breakthrough in medicine has given us the ability to sequence the DNA in cancer cells to identify possible errors in mutations. The impact of the HGP's success was so significant that President Barack Obama initiated a very ambitious new 'precision medicine' research initiative and announced the launch of this project during his State of the Union Address in 2015. The benefits of precision and personalized medicine include predicting susceptibility to diseases, improving disease diagnostics, preempting disease progression, customizing disease prevention strategies, and developing personalized drugs and therapies. As examples of emerging therapies, we have discussed the role of biomolecules and biologics in precision medicine applications like 'The All of Us,' personalized medicine approaches for monogenic diseases like hemophilia, sickle cell disease, and other rare genetic disorders, and CRISPR gene-editing technologies. Biomolecules play an essential role in all life processes, a variety of signaling processes, which are vital for normal functioning of physiological responses, in the early diagnosis of risk factors for various diseases, in the development of diseases and their progress. Furthermore, biomolecules, RNAs, DNAs, molecular and cellular engineering, genetic engineering of biologics, cells, tissues, and organs, play an important role in emerging therapeutic applications. The majority of the therapies discussed in this review are regulated as biologics under the Public Health Services Act of the USA. There is great interest in developing targeted therapy or precision medicine therapy for monogenic diseases, organ transplant applications, and tumor management, designed to interfere with targeted molecules for cancer-causing genes to slow the spread of cancer cells. Because molecular engineering, the development of biologics, gene-editing applications, and biomanufacturing are key components of emerging therapies, a keynote series was organized at INTERPHEX in November of 2021. INTEPHEX is the premier event that offers the latest intelligence, cutting-edge technologies, and state-of-the-art innovation for product development for pharmaceutical and biotechnology platforms. In an earlier article in this journal, we described drug discovery and development in the COVID Age; this overview provides a birds-eye view of the salient findings in each emerging area of medicine—precision medicine, personalized medicine, and emerging therapies.

Keywords: 
SARS-CoV-2 • COVID-19 • biomolecules • precision medicine • personalized medicine
References: 
  1. Pak A, Adegboye OA, Adekunle AI, Rahman KM, McBryde ES, Eisen DP. Economic Consequences of the COVID-19 Outbreak: the Need for Epidemic Preparedness. Front Public Health. 2020 May 29;8:241. doi: 10.3389/fpubh.2020.00241.
  2. Blumenthal D, Fowler EJ, Abrams M, Collins SR. Covid-19 - Implications for the Health Care System. N Engl J Med. 2020 Oct 8;383(15):1483-1488. doi: 10.1056/NEJMsb2021088. Epub 2020 Jul 22. Erratum in: N Engl J Med. 2020 Jul 23;: PMID: 32706956.
  3. Rao GHR. SARS-CoV-2 biochemistry, Transmission, Clinical Manifestations and Prevention. International Journal of Biomedicine. 2020;10(4):303-311. doi: 10.21103/Article10(4)_GE
  4. Rao GHR: Biomedicine in the COVID Age: Opportunities, Responses, and Challenges. International Journal of Biomedicine. 2021;11(3):241-249. doi: 10.21103/Article11(3)_RA1
  5. Institute of Medicine (US) Forum on Microbial Threats. Microbial Evolution and Co-Adaptation: A Tribute to the Life and Scientific Legacies of Joshua Lederberg: Workshop Summary. Washington (DC): National Academies Press (US); 2009. PMID: 20945572.
  6. Lederberg J. Infectious history. Science. 2000 Apr 14;288(5464):287-93. doi: 10.1126/science.288.5464.287.
  7. Taubenberger JK, Morens DM. 1918 Influenza: the mother of all pandemics. Emerg Infect Dis. 2006 Jan;12(1):15-22. doi: 10.3201/eid1201.050979.
  8. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018 Apr;17(4):261-279. doi: 10.1038/nrd.2017.243. 
  9. Damase TR, Sukhovershin R, Boada C, Taraballi F, Pettigrew RI, Cooke JP. The Limitless Future of RNA Therapeutics. Front Bioeng Biotechnol. 2021 Mar 18;9:628137. doi: 10.3389/fbioe.2021.628137.
  10. Landrier JF, Derghal A, Mounien L. MicroRNAs in Obesity and Related Metabolic Disorders. Cells. 2019 Aug 9;8(8):859. doi: 10.3390/cells8080859.
  11. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015 Feb 26;372(9):793-5. doi: 10.1056/NEJMp1500523.
  12. Jameson JL, Longo DL. Precision medicine--personalized, problematic, and promising. N Engl J Med. 2015 Jun 4;372(23):2229-34. doi: 10.1056/NEJMsb1503104.
  13. All of Us Research Program Investigators, Denny JC, Rutter JL, Goldstein DB, Philippakis A, Smoller JW, Jenkins G, Dishman E. The "All of Us" Research Program. N Engl J Med. 2019 Aug 15;381(7):668-676. doi: 10.1056/NEJMsr1809937. 
  14. Kim J, Hu C, Moufawad El Achkar C, Black LE, Douville J, et al. Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease. N Engl J Med. 2019 Oct 24;381(17):1644-1652. doi: 10.1056/NEJMoa1813279. 
  15. Hayden EC. If DNA is Like a Software, Can We Fix the Code? MIT Technology Reviews. 123 (2):47-49, 2020.
  16. Roedder S, Vitalone M, Khatri P, Sarwal MM. Biomarkers in solid organ transplantation: establishing personalized transplantation medicine. Genome Med. 2011 Jun 8;3(6):37. doi: 10.1186/gm253.
  17. Gerrard JM, Stuart MJ, Rao GH, Steffes MW, Mauer SM, Brown DM, White JG. Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats. J Lab Clin Med. 1980 Jun;95(6):950-8. 
  18. Drew L. How stem cells could fix type-1 diabetes. Nature. 2021;595:s64-s66. doi: 10.1038/d41586-021-01842-x
  19. Youle RJ, Neville DM Jr. Anti-Thy 1.2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5483-6. doi: 10.1073/pnas.77.9.5483.
  20. Wu M, Brown WL, Stockley PG. Cell-specific delivery of bacteriophage-encapsidated ricin A chain. Bioconjug Chem. 1995 Sep-Oct;6(5):587-95. doi: 10.1021/bc00035a013. 
  21. Ko YH, Verhoeven HA, Lee MJ, Corbin DJ, Vogl TJ, Pedersen PL. A translational study "case report" on the small molecule "energy blocker" 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside. J Bioenerg Biomembr. 2012 Feb;44(1):163-70. doi: 10.1007/s10863-012-9417-4. 
  22. Li HJ, Du JZ, Du XJ, Xu CF, Sun CY, Wang HX, Cao ZT, Yang XZ, Zhu YH, Nie S, Wang J. Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4164-9. doi: 10.1073/pnas.1522080113. 
  23. Ansari D, Friess H, Bauden M, Samnegård J, Andersson R. Pancreatic cancer: disease dynamics, tumor biology and the role of the microenvironment. Oncotarget. 2018 Jan 6;9(5):6644-6651. doi: 10.18632/oncotarget.24019. 
  24. Cook KM, Figg WD. Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin. 2010 Jul-Aug;60(4):222-43. doi: 10.3322/caac.20075. 
  25. Marshall HT, Djamgoz MBA. Immuno-Oncology: Emerging Targets and Combination Therapies. Front Oncol. 2018 Aug 23;8:315. doi: 10.3389/fonc.2018.00315. 
  26. Ventola CL. Cancer Immunotherapy, Part 3: Challenges and Future Trends. P T. 2017 Aug;42(8):514-521. 
  27. Delgado MD, León J. Gene expression regulation and cancer. Clin Transl Oncol. 2006 Nov;8(11):780-7. doi: 10.1007/s12094-006-0132-7.
  28. Kagohara LT, Stein-O'Brien GL, Kelley D, Flam E, Wick HC, Danilova LV, Easwaran H, Favorov AV, Qian J, Gaykalova DA, Fertig EJ. Epigenetic regulation of gene expression in cancer: techniques, resources and analysis. Brief Funct Genomics. 2018 Jan 1;17(1):49-63. doi: 10.1093/bfgp/elx018. 
  29. Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017 Jun;23(6):703-713. doi: 10.1038/nm.4333. Epub 2017 May 8. Erratum in: Nat Med. 2017 Aug 4;23 (8):1004. 
  30. Sun Y. Tumor microenvironment and cancer therapy resistance. Cancer Lett. 2016 Sep 28;380(1):205-15. doi: 10.1016/j.canlet.2015.07.044.
  31. Lasfar A, Balan M, Cohen-Solal KA, Zloza A. Editorial: Tumor Microenvironment and Resistance to Current Therapies. Front Oncol. 2019 Nov 14;9:1131. doi: 10.3389/fonc.2019.01131. 
  32. Wu P, Gao W, Su M, Nice EC, Zhang W, Lin J, Xie N. Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment. Front Cell Dev Biol. 2021 Mar 1;9:641469. doi: 10.3389/fcell.2021.641469. 
  33. Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduct Target Ther. 2020 Jan 3;5(1):1. doi: 10.1038/s41392-019-0089-y. 
  34. Cornu TI, Mussolino C, Cathomen T. Refining strategies to translate genome editing to the clinic. Nat Med. 2017 Apr 3;23(4):415-423. doi: 10.1038/nm.4313.
  35. Wang X, Tokheim C, Gu SS, Wang B, Tang Q, Li Y, Traugh N, Zeng Z, Zhang Y, Li Z, Zhang B, Fu J, Xiao T, Li W, Meyer CA, Chu J, Jiang P, Cejas P, Lim K, Long H, Brown M, Liu XS. In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target. Cell. 2021 Oct 14;184(21):5357-5374.e22. doi: 10.1016/j.cell.2021.09.006. 
  36. Chu VT, Graf R, Wirtz T, Weber T, Favret J, Li X, Petsch K, Tran NT, Sieweke MH, Berek C, Kühn R, Rajewsky K. Efficient CRISPR-mediated mutagenesis in primary immune cells using CrispRGold and a C57BL/6 Cas9 transgenic mouse line. Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12514-12519. doi: 10.1073/pnas.1613884113. 
  37. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013 Nov;8(11):2281-2308. doi: 10.1038/nprot.2013.143. 
  38. Azangou-Khyavy M, Ghasemi M, Khanali J, Boroomand-Saboor M, Jamalkhah M, Soleimani M, Kiani J. CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer. Front Immunol. 2020 Sep 29;11:2062. doi: 10.3389/fimmu.2020.02062.
  39. Chira S, Gulei D, Hajitou A, Berindan-Neagoe I. Restoring the p53 'Guardian' Phenotype in p53-Deficient Tumor Cells with CRISPR/Cas9. Trends Biotechnol. 2018 Jul;36(7):653-660. doi: 10.1016/j.tibtech.2018.01.014. 
  40. Joung J, Konermann S, Gootenberg JS, Abudayyeh OO, Platt RJ, Brigham MD, Sanjana NE, Zhang F. Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening. Nat Protoc. 2017 Apr;12(4):828-863. doi: 10.1038/nprot.2017.016.
  41. Chen S, Sanjana NE, Zheng K, Shalem O, Lee K, Shi X, Scott DA, Song J, Pan JQ, Weissleder R, Lee H, Zhang F, Sharp PA. Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell. 2015 Mar 12;160(6):1246-60. doi: 10.1016/j.cell.2015.02.038. 
  42. Raper V. To Root Out Cancer Immunotherapies Dig Deeper. Gen Eng. & Biotech News. 2017;38(1) December 26.
  43. Raita Y, Camargo CA Jr, Liang L, Hasegawa K. Big Data, Data Science, and Causal Inference: A Primer for Clinicians. Front Med (Lausanne). 2021 Jul 6;8:678047. doi: 10.3389/fmed.2021.678047. 
  44. Tejera P, Jardim J, Laucho-Contreras ME. Editorial: Precision Medicine in Pulmonary Diseases-Same Principles, New Approach. Front Med (Lausanne). 2021 Dec 20;8:821013. doi: 10.3389/fmed.2021.821013.
  45. Guzmán-Vargas J, Ambrocio-Ortiz E, Pérez-Rubio G, Ponce-Gallegos MA, Hernández-Zenteno RJ, Mejía M, Ramírez-Venegas A, Buendia-Roldan I, Falfán-Valencia R. Differential Genomic Profile in TERT, DSP, and FAM13A Between COPD Patients With Emphysema, IPF, and CPFE Syndrome. Front Med (Lausanne). 2021 Aug 19;8:725144. doi: 10.3389/fmed.2021.725144.
  46. Goetz LH, Schork NJ. Personalized medicine: motivation, challenges, and progress. Fertil Steril. 2018 Jun;109(6):952-963. doi: 10.1016/j.fertnstert.2018.05.006. 
  47. Sverdlov O, van Dam J, Hannesdottir K, Thornton-Wells T. Digital Therapeutics: An Integral Component of Digital Innovation in Drug Development. Clin Pharmacol Ther. 2018 Jul;104(1):72-80. doi: 10.1002/cpt.1036. 
  48. Tate, AR, Rao GHR: Activity Trackers, Wearables, Noninvasive Technologies for Early Detection, and Management of Cardiometabolic Risks. International Journal of Biomedicine. 2020;10(3):189-197. doi: 10.21103/Article10(3)_RA2
  49. Dzobo K. Taking a Full Snapshot of Cancer Biology: Deciphering the Tumor Microenvironment for Effective Cancer Therapy in the Oncology Clinic. OMICS. 2020 Apr;24(4):175-179. doi: 10.1089/omi.2020.0019.
  50. Errington TM, Denis A, Perfito N, Iorns E, Nosek BA. Challenges for assessing replicability in preclinical cancer biology. Elife. 2021 Dec 7;10:e67995. doi: 10.7554/eLife.67995.

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