Therapeutic fusion proteins are a class of hybrid constructs that combine distinct biomolecules into a single platform with the additive effects of the components. The ability to fuse two unrelated proteins provides a means to localize mechanisms to better treat a range of diseases. Fusion proteins can be designed to impart diverse functions, including increasing half-life, providing targeting, and enabling sustained signaling. Of these, half-life extenders, which are fused to a therapeutic protein to increase exposure, are the most established group of fusion proteins, with many clinical successes. Rapid advances in antibody and antibody-derivative technology have enabled the fusion of targeting domains with therapeutic proteins. An emerging group of therapeutic fusion proteins has two separate active functions. Although most research for therapeutic fusion proteins focuses on cancer, prior successes provide a foundation for studies into other diseases as well. The exponential emergence of biopharmaceuticals gives precedence for increased research into therapeutic fusion proteins for a multitude of diseases.
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http://dx.doi.org/10.1208/s12248-023-00873-8 | DOI Listing |
Chem Rev
January 2025
Freie Universität Berlin, Institute of Chemistry and Biochemistry, 14195 Berlin, Germany.
Throughout history, we have looked to nature to discover and copy pharmaceutical solutions to prevent and heal diseases. Due to the advances in metabolic engineering and the production of pharmaceutical proteins in different host cells, we have moved from mimicking nature to the delicate engineering of cells and proteins. We can now produce novel drug molecules, which are fusions of small chemical drugs and proteins.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.
View Article and Find Full Text PDFJ Virol
January 2025
National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Coronaviruses are characterized by their progeny assembly and budding in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). Our previous studies demonstrated that truncation of 9 amino acids in the cytoplasmic tail (CT) of the infectious bronchitis virus (IBV) spike (S) protein impairs its localization to the ERGIC, resulting in increased expression at the plasma membrane. However, the precise mechanism underlying this phenomenon remained elusive.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. China.
Pesticides and plastics have brought convenience to agricultural production and daily life, but they have also led to environmental pollution through residual chemicals. Emamectin benzoate (EMB) is among the most widely used insecticides, which can cause environmental pollution and harm the health of organisms. Additionally, microplastics (MPs), a relatively new type of pollutant, not only are increasing in residual amounts within water bodies and aquatic organisms but also exacerbate pollution by adsorbing other pollutants, leading to a mixed pollution scenario.
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