An economical, effective and biocompatible gene therapy strategy promotes cardiac repair

July 6, 2012

Dr Changfa Guo, Professor Chunsheng Wang and their co-investigators from Zhongshan hospital Fudan University, Shanghai, China have established a novel hyperbranched poly(amidoamine) (hPAMAM) nanoparticle based hypoxia regulated vascular endothelial growth factor (HRE-VEGF) gene therapy strategy which is an excellent substitute for the current expensive and uncontrollable VEGF gene delivery system. This discovery, reported in the June 2012 issue of Experimental Biology and Medicine, provides an economical, feasible and biocompatible gene therapy strategy for cardiac repair.

Transplantation of VEGF gene manipulated mesenchymal stem cells (MSCs) has been proposed as a promising therapeutic method for cardiac repair after myocardium infarction. However, the gene delivery system, including the VEGF gene and delivery vehicle, needs to be optimized. On one hand, long-term and uncontrollable VEGF over-expression in vivo has been observed to lead to hemangioma formation instead of functional vessels in animal models. On the other hand, though non- vector can circumvent the limitations of virus, drawbacks of the current non-, such as complex synthesis procedure, limited transfection efficiency and high cytotoxicity, still needs to be overcome.

Co-investigators, Drs. Kai Zhu and Hao Lai, said "Hypoxia response elements were inserted into the promoter region of VEGF gene to form HRE-VEGF, which provided a safer alternative to the conventionally available VEGF gene". "The HRE-VEGF up-regulates under caused by ischemic myocardium and turns it off under normoxia condition when the regional is adequate."

The hPAMAM nanoparticles, which exhibit high gene transfection efficiency and low cytotoxicity during the gene delivery process, can be synthesized by a simpler and more economical one-step/pot polymerization technique. Drs. Zhu and Lai, said "Using the hPAMAM based gene delivery approach, our published and unpublished results explicitly demonstrated that it was an economical, effective and biocompatible gene delivery vehicle".

Dr Guo concluded that "Treatment with hPAMAM-HRE-VEGF transfected MSCs after myocardium infarction improved the myocardial VEGF level, which improved graft MSC survival, increased neovascularization and ultimately improved heart function. And this novel VEGF gene delivery system may have clinical relevance for tissue repair in other ischemic diseases".

Dr. Steve Goodman, Editor-in-Chief of said "Guo and colleagues have provided an exciting new nanoparticle based gene therapy for cardiac repair. This novel approach has great promise for repair of the heart after myocardial infarction."

Explore further: Promising new approach to treating debilitating nervous system disease

Related Stories

High VEGF signaling score tied to lung cancer prognosis

February 22, 2012

(HealthDay) -- A high vascular endothelial growth factor (VEGF) signaling score correlates with good prognosis in patients with early squamous cell carcinoma (SCC) of the lung, according to a study published online Feb. 21 ...

A culprit behind brain tumor resistance to therapy

March 5, 2012

Persistent protein expression may explain why tumors return after therapy in glioblastoma patients, according to a study published on March 5th in the Journal of Experimental Medicine.

Recommended for you

Anti-tumor antibodies could counter atherosclerosis, study finds

July 20, 2016

Investigators at the Stanford University School of Medicine have learned the signal that tumor cells display on their surfaces to protect themselves from being devoured by the immune system also plays a role in enabling atherosclerosis, ...

A more powerful way to develop therapeutics?

July 21, 2016

A University of Toronto scientist has developed a new method for identifying the raw ingredients necessary to build 'biologics', a powerful class of medications that has revolutionized treatment of diseases like rheumatoid ...

New algorithm characterizes how cancer genomes get scrambled

July 21, 2016

A new method for analyzing the scrambled genomes of cancer cells gives researchers for the first time the ability to simultaneously identify two different types of genetic changes associated with cancers and to identify connections ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.