Development of IFNβ-1a versions with reduced immunogenicity and full in vitro biological activity for the treatment of multiple sclerosis.

IFNβ (recombinant interferon Beta) has been widely used for the treatment of Multiple sclerosis for the last four decades. Despite the human origin of the IFNβ sequence, IFNβ is immunogenic, and unwanted immune responses in IFNβ-treated patients may compromise its efficacy and safety in the clinic. In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNβ-1a.

Development of highly stable and de-immunized versions of recombinant alpha interferon: Promising candidates for the treatment of chronic and emerging viral diseases.

Human interferon alpha (hIFN-α) administration constitutes the current FDA approved therapy for chronic Hepatitis B and C virus infections. Additionally, hIFN-α treatment efficacy was recently demonstrated in patients with COVID-19. Thus, hIFN-α constitutes a therapeutic alternative for those countries where vaccination is inaccessible and for people who did not respond effectively to vaccination.

Development of Magoh protein-overexpressing HEK cells for optimized therapeutic protein production.

In the pharmaceutical industry, the need for high levels of protein expression in mammalian cells has prompted the search for new strategies, including technologies to obtain cells with improved mechanisms that enhance its transcriptional activity, folding, or protein secretion. Chinese Hamster Ovary (CHO) cells are by far the most used host cell for therapeutic protein expression. However, these cells produce specific glycans that are not present in human cells and therefore potentially immunogenic.

Multiplexed Gene Expression as a Characterization of Bioactivity for Interferon Beta (IFN-β) Biosimilar Candidates: Impact of Innate Immune Response Modulating Impurities (IIRMIs).

Recombinant human interferon-β (rhIFN-β) therapy is the first-line treatment in relapsing-remitting forms of multiple sclerosis (MS). The mechanism of action underlying its therapeutic activity is only partially understood as IFN-βs induce the expression of over 1000 genes modifying multiple immune pathways. Currently, assessment of potency for IFN-β products is based on their antiviral effect, which is not linked to its therapeutic effect.

De-immunized and Functional Therapeutic (DeFT) versions of a long lasting recombinant alpha interferon for antiviral therapy.

Interferon α (IFN-α) exerts potent antiviral, immunomodulatory, and antiproliferative activity and have proven clinical utility in chronic hepatitis B and C virus infections. However, repeated IFN-α administration induces neutralizing antibodies (NAb) against the therapeutic in a significant number of patients. Associations between IFN-α immunogenicity and loss of efficacy have been described.

Development of lentiviral vectors for transient and stable protein overexpression in mammalian cells. A new strategy for recombinant human FVIII (rhFVIII) production.

Background: Recombinant protein overexpression in mammalian cells constitutes a real challenge in therapeutic protein production. Following the discovery of intron functionality in gene expression, various expression vectors that include them in their sequences have been developed. In this study, the main goal was to develop new lentiviral vectors (LVs) carrying different promoter and intron-containing 5'UTR (5' untranslated region) combinations and the design of LVs for rhFVIII production in Chinese hamster ovary (CHO) cells.

Functional interconnections of Arabidopsis exon junction complex proteins and genes at multiple steps of gene expression.

The exon junction complex (EJC) is deposited on mRNA after splicing and participates in several aspects of RNA metabolism, from intracellular transport to translation. In this work, the functional and molecular interactions of Arabidopsis homologues of Mago, Y14, and PYM, three EJC components that participate in intron-mediated enhancement of gene expression in animals, have been analysed. AtMago, AtY14, and AtPYM are encoded by single genes that show similar expression patterns and contain common regulatory elements, known as site II, that are required for expression.

Common sets of promoter elements determine the expression characteristics of three Arabidopsis genes encoding isoforms of mitochondrial cytochrome c oxidase subunit 6b.

The promoters of the three Arabidopsis nuclear genes encoding mitochondrial cytochrome c oxidase subunit 6b (AtCOX6b) have similar expression patterns, with preferential expression in anthers and meristems, and are induced by sucrose and etiolation. Additionally, induction of AtCOX6b-1 by GA(3) and AtCOX6b-3 by 6-benzylaminopurine was observed. Site II elements (TGGGCC/T) present in the three promoters bind common nuclear proteins and are important for basal and induced expression.

Transcriptional coordination of the biogenesis of the oxidative phosphorylation machinery in plants.

Publicly available microarray experiments were used to analyze Arabidopsis thaliana genes whose expression is correlated with that of nuclear genes encoding components of the oxidative phosphorylation machinery (OxPhos genes). This analysis indicated the existence of coordination in the expression of genes encoding components of the five respiratory complexes. For these genes, preferential expression was observed in anthers and roots, especially in the elongation zone, while reduced or very low relative expression was evident in leaves and mature pollen grains.