Expanding Horizons: The Diverse Applications of Recombinant Proteins in Medicine

Understanding the Role of Recombinant Proteins in Medical Science

Over the past few centuries, many severe diseases such as cancer, leukemia, and systemic lupus erythematosus have remained elusive, causing pain and suffering for countless individuals. Yet, as science and technology continue to innovate, effective treatments for numerous diseases have been developed. In the midst of this journey, recombinant protein technology has emerged as a significant milestone in the medical field, pushing conventional limits and revealing incredible opportunities.

Recombinant proteins are proteins synthesized in foreign host cells via genetic engineering techniques. Target genes are introduced into host cells, where they undergo transcription and translation processes to facilitate the synthesis of the desired proteins. Recombinant proteins have extensive utility across various domains, with the medical field being a particularly prominent area of application. They are employed in drug and treatment development, comprising a diverse array of substances such as antibodies, hormones, growth factors, and enzymes. Among these, the utilization of recombinant antibodies stands out as one of the prevalent applications, finding use in the treatment of various ailments, including but not limited to cancer, autoimmune disorders, infectious diseases, and more.

Now, when discussing recombinant proteins, it is essential to talk about two popular treatment methods: cell therapy and gene therapy.

Therapeutic Applications of Recombinant Proteins

Recombinant proteins hold considerable promise in the medical field. As scientific and technological advancements continue, and as research into protein engineering deepens, the application of recombinant protein technology in medicine is set to expand and enhance further.

Firstly, recombinant proteins can be used to treat diseases. Through the power of genetic engineering, researchers can create recombinant proteins with precise functions, including antibodies, growth factors, and hormones. For example, Recombinant Human Granulocyte Colony-Stimulating Factor can be used to treat neutropenia caused by myelosuppression[1]; Recombinant Human Erythropoietin can be used to treat anemia caused by chronic renal insufficiency to stimulate red blood cell production and improve hemoglobin levels[2]; Recombinant Human Interleukin-6 Receptor Antagonist can be used to treat inflammatory diseases such as rheumatoid arthritis[3]. These customized proteins hold the potential for treating a myriad of diseases, ranging from cancer and immune system disorders to genetic disorders, among numerous others.

Secondly, recombinant proteins play an integral role in drug development. Many drugs work by interacting with specific proteins. These proteins can also be used as drug targets for screening and evaluating drug effectiveness and safety. For example, Rituximab can be used to treat immune-related diseases such as non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis[4]; Recombinant human growth hormone can be used to treat growth hormone deficiency, short stature in children, Turner syndrome, and so on[5]; Recombinant Factor VIII can be used to treat hemophilia A, supplementing the coagulation function in patients lacking Factor VIII, and more[6]. These drugs have played a key role in the treatment of many severe diseases.

Lastly, recombinant proteins hold significant potential in the fields of tissue engineering and regenerative medicine. Growth factors, bioactive proteins, cell-inducing factors, and others contribute to the restoration and replacement of damaged tissues, thereby stimulating tissue regeneration and repair mechanisms. The application of these recombinant proteins offers essential tools and methodologies for tissue engineering and regenerative medicine, promoting tissue repair and regeneration, and improving disease treatment and patient recovery. As technology continues to develop and research deepens, we can expect more innovations and advancements in this field, brought forth by recombinant proteins.

The Pivotal Role of Recombinant Proteins in Cell Therapy

Cell therapy involves the use of autologous or allogeneic cells to treat disease. This approach entails collecting cells from a patient, which are then genetically modified, expanded or activated to confer a therapeutic effect. After these modifications, the cells are reintroduced into the patient with therapeutic goals such as repairing damaged tissue, restoring organ function, or enhancing the immune response. CAR-T cell therapy, a revolutionary immunotherapy that re-engineers the patient's own T cells to express a specific chimeric antigen receptor (CAR) for identifying and eliminating cancer cells, is one of the most prominent examples of cell therapies. Approved CAR-T cell therapies like Kymriah (tisagenlecleucel), Yescarta (axicabtagene ciloleucel), Tecartus (brexucabtagene autoleucel), and Breyanzi (lisocabtagene maraleucel) have marked important milestones, offering new treatment options for specific types of cancer patients.

Many cell therapies, either invented or being researched, leverage the potential of recombinant proteins. These proteins can enhance treatment effectiveness and improve the success rate of cell therapy. Elements such as cell growth factors, cytokine regulators, and cell signal regulatory molecules play significant roles. Research has shown that cell therapy has made remarkable progress in treating conditions like skin melanoma[7], brain tumors[8], and others. As research continues and clinical practice deepens, cell therapy holds the promise of providing more effective and personalized methods for treating a diverse array of diseases.

Exploring the Potentials of Gene Therapy with Recombinant Proteins

The objective of gene therapy is to address disease by correcting or substituting faulty genes through the introduction of specific genes into patients. This procedure entails delivering the desired gene into the patient's cells using a gene transduction system, which enables the expression of the desired functional protein. Gene therapy shows potential in treating monogenic genetic disorders, cancer, and various chronic ailments. Among them, gene editing is one of the most popular gene therapy methods at present. It is a technology used to modify the genome of cells or organisms. One of the most commonly used methods is the CRISPR-Cas9 system. The goal of gene editing is to correct or change specific genetic characteristics of cells or organisms or the expression of disease-related genes by precisely inserting, deleting or modifying gene sequences.The CRISPR-Cas9 system is currently one of the most commonly used gene editing technologies. It uses a DNA sequence called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the enzyme Cas9 to achieve gene editing. The CRISPR sequence can be combined with a specific guide RNA (gRNA) sequence to form an RNA-DNA complex that guides the Cas9 enzyme to recognize and cut specific genomic DNA. In this way, researchers can use the CRISPR-Cas9 system to delete, insert or modify target gene sequences. Gene editing technology has great potential, and rational use will benefit mankind a lot.

Recombinant protein technology has considerably advanced the research and development in gene therapy. By introducing normal genes and their corresponding recombinant proteins, it's possible to rectify malfunctioning genes and restore normal cellular or tissue physiological processes. Recombinant proteins can also be used as signaling molecules to regulate intercellular signal transduction. Examples include growth factors to promote cell proliferation and repair damaged tissues, and hormones to regulate body metabolism and physiological functions. The use of recombinant proteins in gene therapy provides powerful tools for treating genetic defects, modulating cell signaling, and enhancing immune responses. Recent research has demonstrated progress in gene therapy for the treatment of conditions like Severe Combined Immunodeficiency-X-Linked (SCID—X1 Disease)[9,10] and hemophilia[11]. As technology continues to advance and our understanding of the mechanisms behind recombinant proteins deepens, we can expect even more significant breakthroughs and advancements in gene therapy.

The Future of Recombinant Proteins in Medicine

In summary, the application of recombinant proteins has brought significant progress and hope to the medical field. The diversity and customization potential of recombinant proteins make them a powerful tool for disease treatment. By synthesizing specific recombinant proteins, researchers can develop drugs targeting specific disease targets, providing more precise and efficient treatments. In addition, recombinant proteins are also widely used in the drug discovery process as candidate substances for drug targets, accelerating the development and introduction of new drugs to the market. In the realms of tissue engineering and regenerative medicine, recombinant proteins play an essential role. They can promote tissue repair and regeneration processes and help restore function to damaged tissue. In combination with biological materials, recombinant proteins can also construct functional artificial tissues and organs, offering more treatment options for the medical community.

With the continuous advancement of technology and deepening of research, our understanding and application of recombinant proteins will continue to expand. The emergence of new types of recombinant proteins and design methods will further broaden their application fields and bring more innovations to medical research and clinical practice. In the future, recombinant proteins will undoubtedly become an indispensable tool for disease treatment, drug discovery, tissue engineering, and regenerative medicine, providing better solutions for human health. We are confident in the future prospects of recombinant proteins and anticipate their increasingly pivotal role in the medical field, leading to substantial benefits for human health.

References

[1]Souza L M , Boone T C , Gabrilove J , et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 232 [2023-06-25]. DOI:10.1126/science.2420009

[2]Eschbach J W , Abdulhadi M H , Browne J K , et al . Recombinant human erythropoietin in anemic patients with end-stage renal disease: results of a phase iii multicenter clinical trial. Annals of Internal Medicine. (1989). 111(12). DOI:10.7326/0003-4819-111-12-992.

[3]Campion G V ,  Lebsack M E ,  Lookabaugh J , et al . Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis. the il-1ra arthritis study group. Arthritis & Rheumatism. (2010).39(7), 1092-1101. DOI:10.1002/art.1780390704.

[4] Furman R R , Sharman J P , Coutre S E , et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. New England Journal of Medicine.(2014).DOI:10.1056/nejmoa1315226.

[5] Salomon F , Cuneo R C , Hesp R ,et al. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. New England Journal of Medicine. 1989. 321(26):1797. DOI:10.1056/NEJM198912283212605

[6]LUSHER J M , ARKIN S, ABILGAARD, et al. Recombinant Factor VIII for the Treatment of Previously Untreated Patients with Hemophilia A.Survey of Anesthesiology. 1993. DOI:10.1097/00132586-199310000-00058.

[7] Ramon Y, Mateo B, Mercedes HJ, et al. Efficacy of t-cell receptor-based adoptive cell therapy in cutaneous melanoma: a meta-analysis. The Oncologist. (2023). (6), 6. DOI：

10.1093/oncolo/oyad078

[8] Fares J, Davis ZB, Rechberger JS, et al. Advances in NK cell therapy for brain tumors. NPJ Precis Oncol. (2023) Feb 15;7(1):17. doi: 10.1038/s41698-023-00356-1. 

[9] Cavazzana-Calvo, & M.. Gene therapy of human severe combined immunodeficiency (scid)-x1 disease. Science. (2000)288(5466), 669-672.

[10] Thornhill, S I , Schambach, A , Howe, S J, et al. Self-inactivating gammaretroviral vectors for gene therapy of x-linked severe combined immunodeficiency. Molecular Therapy, (2008)16(3), 590-598.DOI：10.1038/sj.mt.6300393

[11] Gollomp, K L ,  Doshi, B S , &  Arruda, V R . Gene therapy for hemophilia: progress to date and challenges moving forward. Transfusion and Apheresis Science. (2019).58(5).DOI：10.1016/j.transci.2019.08.012