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The vast regenerative potential of stem cells has laid the foundation for stem cell-based therapies. However, certain challenges limit the application of cell-based therapies. The therapeutic use of cell-free therapy can avoid limitations associated with cell-based therapies. Acellular stem cell-based therapies rely on the use of biological factors released by stem cells, including growth factors and extracellular vesicles such as exosomes. Due to their comparable regenerative potential, acellular therapies may provide a feasible and scalable alternative to stem cell-based therapies. Exosomes are small vesicles secreted by various types of cells, including stem cells. Exosomes contain parent cell-derived nucleic acids, proteins, lipids, and other bioactive molecules. They play an important role in intra-cellular communication and influence the biological characteristics of cells. Exosomes inherit the properties of their parent cells; therefore, stem cell-derived exosomes are of particular interest for applications of regenerative medicine. In comparison to stem cell-based therapy, exosome therapy offers several benefits, such as easy transport and storage, no risk of immunological rejection, and few ethical dilemmas. Unlike stem cells, exosomes can be lyophilized and stored off-the-shelf, making acellular therapies standardized and more accessible while reducing overall treatment costs. Exosome-based acellular treatments are therefore readily available for applications in patients at the time of care. The current review discusses the use of exosomes as an acellular therapy. The review explores the molecular mechanism of exosome biogenesis, various methods for exosome isolation, and characterization. In addition, the latest advancements in bioengineering techniques to enhance exosome potential for acellular therapies have been discussed. The challenges in the use of exosomes as well as their diverse applications for the diagnosis and treatment of diseases have been reviewed in detail. [ABSTRACT FROM AUTHOR]

Cancer encompasses various elements occurring at the cellular and genetic levels, necessitating an immunotherapy capable of efficiently addressing both aspects. T cells can combat cancer cells by specifically recognizing antigens on them. This innate capability of T cells has been used to develop cellular immunotherapies, but most of them can only target antigens through major histocompatibility complexes (MHCs). New gene-editing techniques such as clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-cas9) can precisely edit the DNA sequences. CRISPR-cas9 has made it possible to generate genetically engineered chimeric antigen receptors (CARs) that can overcome the problems associated with old immunotherapies. In chimeric antigen receptor T (CAR-T) cell therapy, the patient's T cells are isolated and genetically modified to exhibit synthetic CAR(s). CAR-T cell treatment has shown remarkably positive clinical outcomes in cancers of various types. Nevertheless, there are various challenges that reduce CAR-T effectiveness in solid tumors. It is required to address these challenges in order to make CAR-T cell therapy a better and safer option. Combining CAR-T treatment with other immunotherapies that target multiple antigens has shown positive outcomes. Moreover, recently generated Boolean logic-gated advanced CARs along with artificial intelligence has expanded its potential to treat solid tumors in addition to blood cancers. This review aims to describe the structure, types, and various methods used to develop CAR-T cells. The clinical applications of CAR-T cells in hematological malignancies and solid tumours have been described in detail. In addition, this discussion has addressed the limitations associated with CAR-T cells, explored potential strategies to mitigate CAR-T-related toxicities, and delved into future perspectives. [ABSTRACT FROM AUTHOR]

Genome editing techniques have potential to revolutionize the field of life sciences. Several limitations associated with traditional gene editing techniques have been resolved with the development of prime editors that precisely edit the DNA without double-strand breaks (DSBs). To further improve the efficiency, several modified versions of prime editing (PE) system have been introduced. Bi-directional PE (Bi-PE), for example, uses two PE guide RNAs enabling broad and improved editing efficiency. It has the potential to alter, delete, integrate, and replace larger genome sequences and edit multiple bases at the same time. This review aims to discuss the typical gene editing methods that offer DSB-mediated repair mechanisms, followed by the latest advances in genome editing technologies with non-DSB-mediated repair. The review specifically focuses on Bi-PE being an efficient tool to edit the human genome. In addition, the review discusses the applications, limitations, and future perspectives of Bi-PE for gene editing.