Transgenic plants for allergen-specific immunotherapy

Allergen-specific immunotherapy （IT） is an effective treatment for allergic diseases. Although subcutane-ous and sublingual ITs are currently used, safer, easier, and more effective IT is under development. Induction of immune tolerance by oral administration of allergen has been proven, though oral IT has not been applied clinically. It is mainly because a large amount of puri-fied allergen is required to induce oral tolerance. To overcome this problem, plants, peculiarly rice, have been investigated as allergen vehicles for oral IT. Rice can store a considerable amount of expressed allergen in its seeds and the accumulated allergen is stable and resistant to gastrointestinal digestion. Therefore, we have developed transgenic rice seeds （Tg rice） in which major epitopes of cedar pollen or house dust mites are expressed. We are establishing Tg rice with dem-onstrated effcacy in murine models of allergic rhinitis and bronchial asthma by oral administration at practical doses. In addition, the amount, distribution, and aller-genicity of the expressed allergen have been improved in our Tg rice. Rice-based oral IT is a promising new concept in IT for the treatment of allergic diseases.

Twins-like nanodrugs synchronously transport in blood and coalesce inside tumors for sensitive ultrasound imaging and triggerable penetrative drug delivery

Nanodrugs capable of aggregating in the tumor microenvironment(TME)have demonstrated great efficiency in improving the therapeutic outcome.Among vari-ous approaches,the strategy utilizing electrostatic interaction as a driving force to achieve intratumor aggregation of nanodrugs has attracted great attention.However,the great difference between the two nanodrugs with varied physicochemical prop-erties makes their synchronous transport in blood circulation and equal-opportunity tumor uptake impossible,which significantly detracts from the beneficial effects of nanodrug aggregation inside tumors.We herein propose a new strategy to construct a pair of extremely similar nanodrugs,referred to as“twins-like nanodrugs(TLNs)”,which have identical physicochemical properties including the same morphology,size,and electroneutrality to render them the same blood circulation time and tumor entrance.The 1:1 mixture of TLNs(TLNs-Mix)intravenously injected into a mouse model efficiently accumulates in tumor sites and then transfers to oppositely charged nanodrugs for electrostatic interaction-driven coalescence via responding to matrix metalloproteinase-2(MMP-2)enriched in tumor.In addition to enhanced tumor retention,the thus-formed micron-sized aggregates show high echo intensity essen-tial for ultrasound imaging as well as ultrasound-triggered penetrative drug delivery.Owing to their distinctive features,the TLNs-Mix carrying sonosensitizer,immune adjuvant,and ultrasound contrast agent exert potent sonodynamic immunotherapy against hypovascular hepatoma,demonstrating their great potential in treating solid malignancies.