Author(s):
Sasikala Chinnappan, Mohamed Suhail, Venkatalakshmi Ranganathan
Email(s):
venkatalakshmi@crescent.education
DOI:
10.52711/0974-360X.2025.00493
Address:
Sasikala Chinnappan1, Mohamed Suhail2, Venkatalakshmi Ranganathan2*
1Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia – 56000.
2Department of Pharmaceutics, Crescent School of Pharmacy, B.S. Abdur Rahman, Crescent Institute of Science and Technology, Chennai - 600048, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 7,
Year - 2025
ABSTRACT:
The burgeoning field of protein engineering has paved the way for innovative developments in the realm of therapeutics. With an increasing understanding of the intricate structure-function relationships of proteins, scientists have harnessed advanced techniques to tailor protein properties, ultimately enhancing their efficacy and specificity in therapeutic applications which shows significant evolution in protein based treatment. This article comprehensively overviews of the recent advancements in protein engineering techniques and their impact on the development of novel therapeutics. Key topics covered include rational design strategies, directed evolution methodologies, and computational modeling approaches, elucidating how these techniques have enabled the precise manipulation of protein structures to achieve desired functional attributes. Additionally, the article highlights notable examples of engineered proteins that have exhibited promising results in preclinical and clinical settings, underscoring the transformative potential of these strategies in addressing challenging diseases and disorders. Thus, this article seeks to elucidate the potential of protein engineering in addressing intricate medical obstacles and promoting the progress of personalized and precision medicine. By shedding light on the latest trends and breakthroughs in protein engineering, this article aims to provide a valuable resource for researchers and professionals in the field, facilitating the continued progress and application of these advanced techniques in therapeutic biochemistry and biotechnology.
Cite this article:
Sasikala Chinnappan, Mohamed Suhail, Venkatalakshmi Ranganathan. In-Depth Review of Advanced Techniques in Protein Engineering in Therapeutic Innovations. Research Journal of Pharmacy and Technology. 2025;18(7):3419-7. doi: 10.52711/0974-360X.2025.00493
Cite(Electronic):
Sasikala Chinnappan, Mohamed Suhail, Venkatalakshmi Ranganathan. In-Depth Review of Advanced Techniques in Protein Engineering in Therapeutic Innovations. Research Journal of Pharmacy and Technology. 2025;18(7):3419-7. doi: 10.52711/0974-360X.2025.00493 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-7-73
10. REFERENCES:
1. Faber MS, Whitehead TA. Data-driven engineering of protein therapeutics. Current Opinion in Biotechnology. 2019; Dec 1; 60: 104-10 https://doi.org/10.1016/j.copbio.2019.01.015
2. Singh DB, Tripathi T, editors. Protein-based Therapeutics. Springer Nature; 2023 Mar 1. https://doi.org/10.1007/978-981-19-8249-1
3. Carter PJ. Introduction to current and future protein therapeutics: a protein engineering perspective. Experimental Cell Research. 2011; May 15; 317(9): 1261-9. https://doi.org/10.1016/j.yexcr.2011.02.013
4. Li Y, Cirino PC. Recent advances in engineering proteins for biocatalysis. Biotechnology and Bioengineering. 2014; Jul; 111(7): 1273-87. https://doi.org/10.1002/bit.25240
5. Hellinga HW. Computational protein engineering. Nature Structural Biology. 1998; Jul; 5(7): 525-7. https://doi.org/10.1038/776
6. Qu G, Li A, Acevedo‐Rocha CG, Sun Z, Reetz MT. The crucial role of methodology development in directed evolution of selective enzymes. Angewandte Chemie International Edition. 2020; Aug 3; 59(32): 13204-31. https://doi.org/10.1002/anie.201901491
7. Kuhlman B, Bradley P. Advances in protein structure prediction and design. Nature Reviews Molecular Cell Biology. 2019; Nov; 20(11): 681-97. https://doi.org/10.1038/s41580-019-0163-x
8. Koga N, Tatsumi-Koga R, Liu G, Xiao R, Acton TB, Montelione GT, Baker D. Principles for designing ideal protein structures. Nature. 2012; Nov 8; 491(7423): 222-7. https://doi.org/10.1038/nature11600
9. S.D. Mankar, Bhagyashri S. Jadhav, Awantika N. Kale. Basics and Recent Advances in Peptide and Protein Drug Delivery. Asian Journal of Pharmacy and Technology. 2023; 13(3): 207-2 https://doi.org/10.52711/2231-5713.2023.00037
10. Akshay R. Yadav, Shrinivas K. Mohite. Recent Advances in Protein and Peptide Drug Delivery. Res. J. Pharma. Dosage Forms and Tech. 2020; 12(3): 205-212. https://doi.org/10.5958/0975-4377.2020.00035.X
11. Marshall SA, Lazar GA, Chirino AJ, Desjarlais JR. Rational design and engineering of therapeutic proteins. Drug Discovery Today. 2003; Mar 1; 8(5): 212-21. 9 https://doi.org/10.1016/S1359-6446(03)02610-2
12. Chevalier A, Silva DA, Rocklin GJ, Hicks DR, Vergara R, Murapa P, Bernard SM, Zhang L, Lam KH, Yao G, Bahl CD. Massively parallel de novo protein design for targeted therapeutics. Nature. 2017; Oct 5; 550(7674): 74-9. https://doi.org/10.1038/nature23912
13. Pace CN, Scholtz JM, Grimsley GR. Forces stabilizing proteins. FEBS Letters. 2014; Jun 27; 588(14): 2177-84. https://doi.org/10.1016/j.febslet.2014.05.006
14. Doyle SK, Pop MS, Evans HL, Koehler AN. Advances in discovering small molecules to probe protein function in a systems context. Current Opinion in Chemical Biology. 2016; Feb 1; 30: 28-36. https://doi.org/10.1016/j.cbpa.2015.10.032
15. Schreiber G, Fleishman SJ. Computational design of protein–protein interactions. Current opinion in structural biology. 2013; Dec 1; 23(6): 903-10. https://doi.org/10.1016/j.sbi.2013.08.003
16. Sameena Mehtab, Harpreet Parmar, Tanveer Irshad Siddiqi, Atanu Singha Roy. Determination of Protein Binding Affinities and Investigation into the Antimicrobial Activities of Cu(II), Co(II) and Ni(II) Mixed Ligand Complexes. Asian J. Research Chem. 2015; 8(2): February 99-107. https://doi.org/10.5958/0974-4150.2015.00018.8
17. Lane MD, Seelig B. Advances in the directed evolution of proteins. Current Opinion in Chemical Biology. 2014; Oct 1; 22: 129-36. https://doi.org/10.1016/j.cbpa.2014.09.013
18. Lutz S. Beyond directed evolution—semi-rational protein engineering and design. Current Opinion in Biotechnology. 2010; Dec 1; 21(6): 734-43.https://doi.org/10.1016/j.copbio.2010.08.011
19. Wójcik M, Telzerow A, Quax WJ, Boersma YL. High-throughput screening in protein engineering: recent advances and future perspectives. International Journal of Molecular Sciences. 2015; Oct 20; 16(10): 24918-45. https://doi.org/10.3390/ijms161024918
20. Vasserot AP, Dickinson CD, Tang Y, Huse WD, Manchester KS, Watkins JD. Optimization of protein therapeutics by directed evolution. Drug Discovery Today. 2003; Jan 21; 8(3): 118-26. https://doi.org/10.1016/S1359-6446(02)02590-4
21. Buchanan A, Ferraro F, Rust S, Sridharan S, Franks R, Dean G, McCourt M, Jermutus L, Minter R. Improved drug-like properties of therapeutic proteins by directed evolution. Protein Engineering, Design and Selection. 2012; Oct 1; 25(10): 631-8. https://doi.org/10.1093/protein/gzs054
22. Alka Singh, Bhaskar Kumar Gupta, Neeraj Upmanyu. A mini Review on Analytical and Bioanlytical Techniques in Study of Drugs-Protein Interaction. Asian Journal of Research in Chemistry. 2024; 17(2): 111-8. https://doi.org/10.52711/0974-4150.2024.00022
23. Susmi M S, Revathy S Kumar, Sreelakshmi V, Sruthy V Menon, Surya Mohan, Saranya Tulasidharan Suja, Sathianarayanan, Asha Asokan Manakadan. A Computational approach for identification of Phytochemicals for targeting and optimizing the inhibitors of Heat shock proteins. Research J. Pharm. and Tech. 2015; 8(9): Sept, 1199-1204 https://doi.org/10.5958/0974-360X.2015.00219.X
24. Derat E, Kamerlin SC. Computational advances in protein engineering and enzyme design. The Journal of Physical Chemistry B. 2022; Apr 7; 126(13): 2449-51. https://doi.org/10.1021/acs.jpcb.2c01198
25. Childers MC, Daggett V. Insights from molecular dynamics simulations for computational protein design. Molecular systems Design and Engineering. 2017; 2(1): 9-33. https://doi.org/10.1039/C6ME00083E
26. Akshay R. Yadav, Shrinivas K. Mohite. Homology Modeling and Generation of 3D-structure of Protein. Res. J. Pharma. Dosage Forms and Tech. 2020; 12(4): 313-320 https://doi.org/10.5958/0975-4377.2020.00052.X
27. Giordano D, Biancaniello C, Argenio MA, Facchiano A. Drug design by pharmacophore and virtual screening approach. Pharmaceuticals. 2022; May 23; 15(5): 646. https://doi.org/10.3390/ph15050646
28. Sathish Kumar Mittapalli, J N Narendra Sharath Chandra, Jay Prakash Soni, Ram Babu Tripathi, Iffath Rizwana. Virtual Screening and Pharmacophore Modeling for discovery of Biologically Active Natural Products as Inhibitors of Odorant-binding Proteins. Asian Journal of Research in Chemistry. 2024; 17(1): 17-4 https://doi.org/10.52711/0974-4150.2024.00004
29. Atkins JD, Boateng SY, Sorensen T, McGuffin LJ. Disorder prediction methods, their applicability to different protein targets and their usefulness for guiding experimental studies. International Journal of Molecular Sciences. 2015; Aug 13; 16(8): 19040-54. https://doi.org/10.3390/ijms160819040
30. Alvizo O, Allen BD, Mayo SL. Computational protein design promises to revolutionize protein engineering. Biotechniques. 2007; Jan; 42(1): 31-9. https://doi.org/10.2144/000112336
31. Elzoghby AO, Samy WM, Elgindy NA. Protein-based nanocarriers as promising drug and gene delivery systems. Journal of Controlled Release. 2012; Jul 10; 161(1): 38-49. https://doi.org/10.1016/j.jconrel.2012.04.036
32. MaHam A, Tang Z, Wu H, Wang J, Lin Y. Protein‐based nanomedicine platforms for drug delivery. Small. 2009; Aug 3; 5(15): 1706-21. https://doi.org/10.1002/smll.200801602
33. Wang G, Uludag H. Recent developments in nanoparticle-based drug delivery and targeting systems with emphasis on protein-based nanoparticles. Expert Opinion on Drug Delivery. 2008; May 1; 5(5): 499-515. https://doi.org/10.1517/17425247.5.5.499
34. Wang J, Shen WC, Zaro JL, editors. Antibody-drug conjugates: the 21st century magic bullets for cancer. New York, NY, USA: Springer; 2015; Mar 5. https://doi.org/10.1007/978-3-319-13081-1
35. Akash MS, Rehman K, Tariq M, Chen S. Development of therapeutic proteins: advances and challenges. Turkish Journal of Biology. 2015; 39(3): 343-58. https://doi.org/10.3906/biy-1411-8
36. Büttel IC, Chamberlain P, Chowers Y, Ehmann F, Greinacher A, Jefferis R, Kramer D, Kropshofer H, Lloyd P, Lubiniecki A, Krause R. Taking immunogenicity assessment of therapeutic proteins to the next level. Biologicals. 2011; Mar 1; 39(2): 100-9. https://doi.org/10.1016/j.biologicals.2011.01.006
37. Eon‐Duval A, Broly H, Gleixner R. Quality attributes of recombinant therapeutic proteins: an assessment of impact on safety and efficacy as part of a quality by design development approach. Biotechnology Progress. 2012; May; 28(3): 608-22. https://doi.org/10.1002/btpr.1548
38. Arindam Chakraborty, Dipak Kumar Singha, Manas Chakraborty, Payel Mukherjee. Protein Therapeutics: An Updated Review. Asian Journal of Research in Pharmaceutical Sciences. 2021; 11(3): 253-7. https://doi.org/10.52711/2231-5659.2021.00040
39. Namdev N., Upadhyay S. Challenges and approaches for Oral protein and peptide drug delivery. Research J. Pharm. and Tech. 2016; 9(3): Mar., 305-312. https://doi.org/10.5958/0974-360X.2016.00056.1
40. Leo DencelinX, Ramkumar T. Distributed Machine Learning Algorithms to classify Protein secondary structures for Drug Design – A Survey. Research J. Pharm. and Tech. 2017; 10(9): 3173-3180 https://doi.org/10.5958/0974-360X.2017.00564.9
41. Niazi SK, Mariam Z. Reinventing Therapeutic Proteins: Mining a treasure of new therapies. Biologics. 2023; Apr 19; 3(2): 72-94. https://doi.org/10.3390/biologics3020005
42. Caravella J, Lugovskoy A. Design of next-generation protein therapeutics. Current Opinion in Chemical Biology. 2010; Aug 1; 14(4): 520-8. https://doi.org/10.1016/j.cbpa.2010.06.175