Utilizing adeno-associated virus as a vector in treating genetic disorders or human cancers.

Clinical data from over two decades, involving more than 3000 treated patients, demonstrate that adeno-associated virus (AAV) gene therapy is a safe, effective, and well-tolerated therapeutic method. Clinical trials using AAV-mediated gene delivery to accessible tissues have led to successful treatments for numerous monogenic disorders and advancements in tissue engineering. Although the US Food and Drug Administration (FDA) has approved AAV for clinical use, systemic administration remains a significant challenge. In this review, we delve into AAV biology, focusing on current manufacturing technologies and transgene engineering strategies. We examine the use of AAVs in ongoing clinical trials for ocular, neurological, and hematological disorders, as well as cancers. By discussing recent advancements and current challenges in the field, we aim to provide valuable insights for researchers and clinicians navigating the evolving landscape of AAV-based gene therapy.

Hispolon Methyl Ether, a Hispolon Analog, Suppresses the SRC/STAT3/Survivin Signaling Axis to Induce Cytotoxicity in Human Urinary Bladder Transitional Carcinoma Cell Lines.

Bladder cancer is a leading human malignancy worldwide. Signal transducer and activator of transcription (STAT) 3 is an oncogenic transcription factor commonly hyperactivated in most human cancers, including bladder cancer. Notably, preclinical evidence has validated STAT3 blockade as a promising therapeutic strategy for bladder cancer. Hispolon Methyl Ether (HME) is a structural analog of hispolon, an anticancer component of the medicinal mushroom Phellinus linteus. Thus far, HME's anticancer activity and mechanisms remain largely unknown. We herein report HME was cytotoxic, more potent than cisplatin, and proapoptotic to various human bladder transitional carcinoma cell lines. Of note, HME blocked STAT3 activation, evidenced by HME-elicited reduction in tyrosine 705-phosphorylated STAT3 levels constitutively expressed or induced by interleukin-6. Significantly, HME-induced cytotoxicity was abrogated in cells expressing a dominant-active STAT3 mutant (STAT3-C), confirming STAT3 blockage as a pivotal mechanism of HME's cytotoxic action. We further revealed that survivin was downregulated by HME, while its levels were rescued in STAT3-C-expressing cells. Moreover, survivin overexpression abolished HME-induced cytotoxicity, illustrating survivin as a central downstream mediator of STAT3 targeted by HME. Lastly, HME was shown to lower tyrosine 416-phosphorylated SRC levels, suggesting that HME inhibits STAT3 by repressing the activation of SRC, a STAT3 upstream kinase. In conclusion, we present the first evidence of HME's anti-bladder cancer effect, likely proceeding by evoking apoptosis through suppression of the antiapoptotic SRC/STAT3/survivin signaling axis.