Jasmonates (JAs) are rapidly induced after wounding and act as key regulators for wound induced signaling pathway. However, what perceives the wound signal and how that triggers JA biosynthesis remains poorly understood. To identify components involved in Arabidopsis wound and JA signaling pathway, we screened for mutants with abnormal expression of a luciferase reporter, which is under the control of a wound-responsive promoter of an ethylene response factor (ERF) transcription factor gene, RAP2.6 (Related to APetala 2.6). The rea1 (RAP2.6 expresser in shoot apex) mutant constitutively expressed the RAP2.6-LUC reporter gene in young leaves. Along with the typical JA phenotypes including shorter petioles, loss of apical dominance, accumulation of anthocyanin pigments and constitutive expression of JA response gene, rea1 plants also displayed cell death and accumulated high levels of JA in response to wounding. The phenotype of rea1 mutant is caused by a gain-of-function mutation in the C-terminus of a mechanosensitive ion channel MscS-like 10 (MSL10). MSL10 is localized in the plasma membrane and is expressed predominantly in root tip, shoot apex and vascular tissues. These results suggest that MSL10 is involved in the wound-triggered early signal transduction pathway and possibly in regulating the positive feedback synthesis of JA.
Nucleic acid (NA)‐based therapy is promising for tissue repair, such as skin and bone defect therapy. However, bacterial infections often occur in the process of tissue healing. The ideal treatment of tissue repair requires both anti‐infection and simultaneous tissue healing. The epidermal growth factor (EGF) plays an important role in wound healing processes. In this work, degradable antibacterial gene vectors based on tobramycin (clinically relevant antibiotic) conjugated poly(aspartic acid) (TPT) are proposed as multifunctional delivery nanosystems of plasmid encoding EGF (pEGF) to realize the antibacterial therapy and tissue healing of infected skin defects. TPT has low cytotoxicity and good degradability, which is helpful in the NA delivery process. TPT demonstrates good transfection performances and hemocompatibility, as well as excellent antibacterial activities in vitro. The outstanding pEGF delivery ability of TPT and the bioactivity of expressed EGF facilitate the proliferation of fibroblast cells. The effective in vivo infected skin defect therapy is also demonstrated with TPT/pEGF nanocomplexes, where skin tissue healing is promoted. The present work opens new avenues for the design of multifunctional delivery nanosystems with antibacterial ability to treat infected tissue defect.
One tumor-targeting, phenylboronic acid-functionalized polyaminoglycoside (SS-HPT-P) was proposed as a safe and effective CRISPR/Cas9 delivery system for the treatment of carcinoma.
An emerging hybrid nanovector integrating the merits of both viral and nonviral vectors has attracted much attention as the next generation of promising gene vectors to overcome the primary challenge of cancer gene therapy. Due to its inherent advantages, lentivirus (Lv) has been increasingly applied and investigated in medical fields. Herein, a new hybrid nanovector (SS‐HPT/Lv) composed of the Lv core and reduction‐responsive hyperbranched polyaminoglycoside (SS‐HPT) shell is designed via electrostatic interaction. In comparison with polybrene (commercial enhanced transfection reagent), SS‐HPT endows the hybrid nanovector with better biosafety. Furthermore, both the appropriate nanoparticle sizes and positive surface potentials contribute to the endocytosis and rescue of SS‐HPT/Lv from endocytic vesicles. Regarding therapeutic application, lentiviral vector acquires permanent transgene expression with the capability of integrating to the host chromosome, and SS‐HPT/Lv exhibits an improved transduction efficacy. The cytosine deaminase/5‐fluorocytosine suicide gene therapy system mediated by SS‐HPT/Lv performs an enhanced antitumor efficiency and extends the survival time of glioma‐bearing rats. Such a hybrid nanovector strategy would open a new avenue to the development of gene vectors for treating malignant cancers.
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