Analysis of Adeno-Associated Virus Serotype 8 (AAV8)-antibody complexes using epitope mapping by molecular imprinting leads to the identification of Fab peptides that potentially evade AAV8 neutralisation.

Gene therapy is a promising approach for treating genetic disorders by delivering therapeutic genes to replace or correct malfunctioning genes. However, the introduced gene therapy vector can trigger an immune response, leading to reduced efficacy and potential harm to the patient. To improve the efficiency and safety of gene therapy, preventing the immune response to the vector is crucial. This can be achieved through the use of immunosuppressive drugs, vector engineering to evade the immune system, or delivery methods that bypass the immune system altogether. By reducing the immune response, gene therapy can deliver therapeutic genes more effectively and potentially cure genetic diseases. In this study, a novel molecular imprinting technique, combined with mass-spectrometry and bioinformatics, was used to identify four antigen-binding fragments (Fab) sequences of Adeno-Associated Virus (AAV) - neutralising antibodies capable of binding to AAV. The identified Fab peptides were shown to prevent AAV8's binding to antibodies, demonstrating their potential to improve gene therapy efficiency by preventing the immune response.

Evading and overcoming AAV neutralization in gene therapy.

Adeno-associated virus (AAV)-derived viral vectors are a promising platform for the delivery of curative, life-changing therapies to a huge number of patients with monogenic disorders. There are currently over 250 clinical trials ongoing worldwide. However, for these therapies to benefit as many patients as possible, techniques must be developed to treat those with pre-existing immunity and to potentially allow re-administration of a dose in the future, should efficacy wane over time. This review discusses the current state and prospects of technologies to evade and overcome these immune responses and allow successful treatment of the greatest number of patients possible.

Varieties of properties: an alternative distinction among qualities.

The traditional distinction between primary (observation independent) and secondary (observation dependent) qualities is not based on a difference that can be sustained in the full light of contemporary scientific understanding. An alternative division of physical and chemical properties is proposed. Like the traditional division of qualities, the alternative system has two main categories. Properties of compound particulars that result from simple combination (e.g., addition) of the properties of their component parts constitute the first class: properties that depend on details of interactions between component parts (e.g. cooperative effects) make up the second type. Application of the alternative dichotomy is considered for the cases of mass (traditionally a primary property) and color (a secondary quality, in the usual division). Both these types of properties can fall in either of the two classes of the alternate division of qualities, depending on the nature of the interaction that occurs between components. Both mass and color show that intermediate cases occur. Application of the alternative categorical scheme is straightforward, but not always simple. The proposed system shows that in chemical combination (and, perforce, in the many more complex systems common in human culture) interactions profoundly influence properties of entities that enter the interaction. This is not adequately treated by philosophical theories of wholes and parts (mereology), which should be extended to apply to such important cases.