What Can De Novo Protein Design Bring to the Treatment of Hematological Disorders?

SIMPLE SUMMARY: Because of the seriousness and complexity of hematological disorders, it is particularly critical to develop new methods for treating them. A protein engineering technique has been used to further enhance therapeutic effects and minimize side effects of protein-based therapeutics. However, the essence of the protein engineering technique is to modify and/or ameliorate natural existing proteins. In recent years, de novo proteins have been developed at a high speed, and their applications in the biomedical field are increasing, including in developing novel diagnostic and therapeutic drugs, novel vaccine techniques, and novel biological materials. At the same time, de novo proteins have also been applied to improve the efficacy of treatment methods in hematological disorders, such as designing the novel structures of chimeric antigen receptors, new inhibitors for treating chronic myeloid leukemia, and the novel type of interleukin-2. Therefore, the purpose of our review is to summarize the recent development of de novo protein design and its application in biomedicine, especially in exploring new treatment methods for hematological disorders. ABSTRACT: Protein therapeutics have been widely used to treat hematological disorders. With the advent of de novo protein design, protein therapeutics are not limited to ameliorating natural proteins but also produce novel protein sequences, folds, and functions with shapes and functions customized to bind to the therapeutic targets. De novo protein techniques have been widely used biomedically to design novel diagnostic and therapeutic drugs, novel vaccines, and novel biological materials. In addition, de novo protein design has provided new options for treating hematological disorders. Scientists have designed protein switches called Colocalization-dependent Latching Orthogonal Cage–Key pRoteins (Co-LOCKR) that perform computations on the surface of cells. De novo designed molecules exhibit a better capacity than the currently available tyrosine kinase inhibitors in chronic myeloid leukemia therapy. De novo designed protein neoleukin-2/15 enhances chimeric antigen receptor T-cell activity. This new technique has great biomedical potential, especially in exploring new treatment methods for hematological disorders. This review discusses the development of de novo protein design and its biological applications, with emphasis on the treatment of hematological disorders.