Progress in Protein Therapeutics

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 2214

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Interests: systems biology; precision medicine; systems pharmacology
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Special Issue Information

Dear Colleagues,

Protein therapeutics play a pivotal role in precision medicine by developing highly targeted treatments customized to the biomolecular profiles and specific disease characteristics of individual patients. By capitalizing on the unique attributes of proteins, such as their capacity for selective binding to particular targets within the body, protein therapeutics can finely regulate disease pathways while mitigating off-target effects. This precision empowers healthcare providers to administer personalized treatments that optimize efficacy and minimize adverse reactions. Through advancements in molecular medicine, protein therapeutics are increasingly being engineered to target specific molecular aberrations underlying diverse complex diseases. In recent years, strides have been made in next-generation monoclonal antibodies, engineering methods for enhanced pharmacokinetics, multifunctional fusion proteins, and innovative delivery methods within the space of protein therapeutics. Ongoing efforts are currently addressing challenges such as immunogenicity, manufacturing complexity, targeting intracellular proteins, and off-target effects to develop more efficacious and precision-medicine-based protein therapeutics.

We are pleased to invite you to contribute original research articles with reference to (but not limited to) new advancements in the design, production, and applications of protein therapeutics and using protein therapeutics for precision medicine practices. We also especially welcome critical review manuscripts with a vision perspective, setting the stage for future research.

Dr. Iman Tavassoly
Guest Editor

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Keywords

  • biologics
  • monoclonal antibodies
  • recombinant proteins
  • therapeutic peptides
  • protein engineering
  • protein therapeutics

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Published Papers (2 papers)

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Research

19 pages, 4166 KiB  
Article
The Plasma Membrane P-Type ATPase CtpA Is Required for Mycobacterium tuberculosis Virulence in Copper-Activated Macrophages in a Mouse Model of Progressive Tuberculosis
by Marcela López-Ruíz, Jorge Barrios-Payán, Milena Maya-Hoyos, Rogelio Hernández-Pando, Marisol Ocampo, Carlos Y. Soto and Dulce Mata-Espinosa
Biomedicines 2025, 13(2), 439; https://doi.org/10.3390/biomedicines13020439 - 11 Feb 2025
Viewed by 839
Abstract
Background/Objective: Finding new targets to attenuate Mycobacterium tuberculosis (Mtb) is key in the development of new TB vaccines. In this context, plasma membrane P-type ATPases are relevant for mycobacterial homeostasis and virulence. In this work, we investigate the role of [...] Read more.
Background/Objective: Finding new targets to attenuate Mycobacterium tuberculosis (Mtb) is key in the development of new TB vaccines. In this context, plasma membrane P-type ATPases are relevant for mycobacterial homeostasis and virulence. In this work, we investigate the role of the copper-transporting P-type ATPase CtpA in Mtb virulence. Methods: The impact of CtpA deletion on Mtb’s capacity to overcome redox stress and proliferate in mouse alveolar macrophages (MH-S) was evaluated, as well as its effect on Mtb immunogenicity. Moreover, the influence of CtpA on the pathogenicity of Mtb in a mouse (BALB/c) model of progressive TB was examined. Results: We found that MH-S cells infected with wild-type (MtbH37Rv) or the mutant strain (MtbH37RvΔctpA) showed no difference in Mtb bacterial load. However, the same macrophages under copper activation (50 µM CuSO4) showed impaired replication of the mutant strain. Furthermore, the mutant MtbΔctpA strain showed an inability to control reactive oxygen species (ROS) induced by PMA addition during MH-S infection. These results, together with the high expression of the Nox2 mRNA observed in MH-S cells infected with the MtbctpA strain at 3 and 6 days post-infection, suggest a potential role for CtpA in overcoming redox stress under infection conditions. In addition, MtbΔctpA-infected BALB/c mice survived longer with significantly lower lung bacterial loads and tissue damage in their lungs than MtbH37Rv-infected mice. Conclusions: This suggests that CtpA is involved in Mtb virulence and that it may be a target for attenuation. Full article
(This article belongs to the Special Issue Progress in Protein Therapeutics)
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16 pages, 5765 KiB  
Article
Investigating the Role of Osteopontin (OPN) in the Progression of Breast, Prostate, Renal and Skin Cancers
by Gautam Kundu and Selvakumar Elangovan
Biomedicines 2025, 13(1), 173; https://doi.org/10.3390/biomedicines13010173 - 13 Jan 2025
Cited by 1 | Viewed by 995
Abstract
Background/Objectives: Cancer is caused by disruptions in the homeostatic state of normal cells, which results in dysregulation of the cell cycle, and uncontrolled growth and proliferation in affected cells to form tumors. Successful development of tumorous cells proceeds through the activation of [...] Read more.
Background/Objectives: Cancer is caused by disruptions in the homeostatic state of normal cells, which results in dysregulation of the cell cycle, and uncontrolled growth and proliferation in affected cells to form tumors. Successful development of tumorous cells proceeds through the activation of pathways promoting cell development and functionality, as well as the suppression of immune signaling pathways; thereby providing these cells with proliferative advantages, which subsequently metastasize into surrounding tissues. These effects are primarily caused by the upregulation of oncogenes, of which SPP1 (secreted phosphoprotein 1), a non-collagenous bone matrix protein, is one of the most well-known. Methods: In this study, we conducted a further examination of the transcriptomic expression profile of SPP1 (Osteopontin) during the progression of cancer in four human tissues, breast, prostate, renal and skin, in order to understand the circumstances conducive to its activation and dysregulation, the biological pathways and other mechanisms involved as well as differences in its splicing patterns influencing its expression and functionality. Results: A significant overexpression of SPP1, as well as a set of other highly correlated genes, was seen in most of these tissues, indicating their extensive implication in cancer. Increased expression was observed with higher tumor stages, especially in renal and skin cancer, while applying therapeutic modalities targeting these genes dampened this effect in breast, prostate and skin cancer. Pathway analyses showed gene signatures related to cell growth and development enriched in tumorigenic conditions and earlier cancer stages, while later stages of cancer showed pathways associated with weakened immune response, in all cancers studied. Moreover, the utilization of therapeutic methods showed the activation of immunogenic pathways in breast, prostate and skin cancer, thereby confirming their viability. Further analyses of differential transcript expression levels in these oncogenes showed their exonic regions to be selectively overexpressed similarly in tumorigenic samples in all cancers studied, while also displaying significant differences in exon selectivity between constituent transcripts, providing a basis for their high degree of multifunctionality in cancer. Conclusions: Overall, this study corroborates the entrenched role of SPP1 in the progression of these four types of cancer, as confirmed by its overexpression and activation of related oncogenes, their co-involvement in key cellular pathways, and predisposition to exhibit differential splicing between their transcripts, while the above effects were found to be highly inhibitable through treatment methods, thereby highlighting its promising role in therapeutic development. Full article
(This article belongs to the Special Issue Progress in Protein Therapeutics)
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