Protein replacement therapy is an umbrella term used for medical treatments that aim to substitute or replenish specific protein deficiencies that result either from the protein being absent or non-functional due to mutations in affected patients. Traditionally, such an approach requires a well characterized but arduous and expensive protein production procedure that employs in vitro expression and translation of the pharmaceutical protein in host cells, followed by extensive purification steps. In the wake of the SARS-CoV-2 pandemic, mRNA-based pharmaceuticals were recruited to achieve rapid in vivo production of antigens, proving that the in vivo translation of exogenously administered mRNA is nowadays a viable therapeutic option. In addition, the urgency of the situation and worldwide demand for mRNA-based medicine has led to an evolution in relevant technologies, such as in vitro transcription and nanolipid carriers. In this review, we present preclinical and clinical applications of mRNA as a tool for protein replacement therapy, alongside with information pertaining to the manufacture of modified mRNA through in vitro transcription, carriers employed for its intracellular delivery and critical quality attributes pertaining to the finished product.

The term “age-associated B cells” (ABCs) refers to a heterogeneous B cell subset (CD19+,CD21−, CD11c+,T-bet+) which is expanded in the elderly, but also accumulates prematurely in patients with autoimmune disorders and/or infectious diseases. In healthy individuals, ABCs represent a low prevalence population that positively impacts immunosenescence. In autoimmunity and infections though, ABCs expand dramatically and produce high titers of antibodies, thus playing a role in the regulation of humoral responses. Despite the fact that these observations were made on both mice and humans, the functional features of ABCs and their exact role in human health and disease are still elusive. This review focuses on ABC and ABC-like sub-populations found in Systemic Lupus Erythematosus (SLE) patients (such as the double negative 2;DN2 population: CD19+,IgD−,CD27−, CXCR5−,T-bet+) and broaches the subject of their potential use as prognostic and/or diagnostic markers. The identification of novel biomarkers, via correlating the cell populations with the clinical profile of the patients, should enable better patient stratification and monitoring. Moreover, the necessity and importance of elucidating the role of transcription factor T-bet (TBX21) in the pathogenesis of human autoimmunity are addressed. T-bet, whose expression is upregulated in both mouse and human ABCs, is considered to play a major role in various aspects of autoimmunity, such as the production of autoreactive IgG, the enhanced antigen presentation to T cells and also the formation of spontaneous germinal centres (GC). Shedding light to its role in human disease, in conjunction with the characterisation of genes and pathways associated with the transcription factor itself, may lead to the discovery of novel druggable targets.

Click on the article title to read more.

Double Negative (DN) B cells constitute a B cell population that lacks expression of immunoglobulin D and CD27 memory marker. These cells expand in elderly healthy individuals, but also accumulate prematurely in autoimmune and infectious diseases.