Rational immunosilencing of a promiscuous T-cell epitope in the capsid of an adeno-associated virus.

Owing to the immunogenicity of adeno-associated viruses (AAVs), gene therapies using AAVs face considerable obstacles. Here, by leveraging ex vivo T-cell assays, the prediction of epitope binding to major histocompatibility complex class-II alleles, sequence-conservation analysis in AAV phylogeny and site-directed mutagenesis, we show that the replacement of amino acid residues in a promiscuous and most immunodominant T-cell epitope in the AAV9 capsid with AAV5 sequences abrogates the immune responses of peripheral blood mononuclear cells to the chimaeric vector while preserving its functions, potency, cellular specificity, transduction efficacy and biodistribution. This rational approach to the immunosilencing of capsid epitopes promiscuously binding to T cells may be applied to other AAV vectors and epitope regions.

Mesoporous Silica Nanoparticles: Properties and Strategies for Enhancing Clinical Effect.

Due to the theragnostic potential of mesoporous silica nanoparticles (MSNs), these were extensively investigated as a novel approach to improve clinical outcomes. Boasting an impressive array of formulations and modifications, MSNs demonstrate significant in vivo efficacy when used to identify or treat myriad malignant diseases in preclinical models. As MSNs continue transitioning into clinical trials, a thorough understanding of the characteristics of effective MSNs is necessary. This review highlights recent discoveries and advances in MSN understanding and technology. Specific focus is given to cancer theragnostic approaches using MSNs. Characteristics of MSNs such as size, shape, and surface properties are discussed in relation to effective nanomedicine practice and projected clinical efficacy. Additionally, tumor-targeting options used with MSNs are presented with extensive discussion on active-targeting molecules. Methods for decreasing MSN toxicity, improving site-specific delivery, and controlling release of loaded molecules are further explained. Challenges facing the field and translation to clinical environments are presented alongside potential avenues for continuing investigations.