The question was asked . . . "what is the limitation of the application of this technology." I can answer that from experience.
You must be sure that when and where you apply any "vascular growth treatment" that there are no tumors or cancers in the region that you are treating AND that your treatment does not travel through the blood or lymph to a remote site that has a tumor or cancer. I was involved with the VEGF studies at SEHMC in Brighton back in the 1990s. They were trying to used VEGF to get coronary artery healing in 7 days. The material and method they used allowed the VEGF to pass through the coronary into the return circulation to the lungs. Guess how many of the people treated for a myocardial infarction had subclinical small cell lung cancer from smoking? Three. They changed the formulation to a non-migrating gel, but the FDA did not ever reverse the clinical hold. Bad for me because I asked the question about migration in conjunction with studies in rabbits and mice. That question got me fired.
But yes, like any clinically valuable treatment . . . there are limitations.
Yes but one could also imagine, since it is plasmid based, a tissue specific promoter for the tissue of interest (in this case muscle), which should limit systemic toxicity and non-specificity of the drug. Local intra muscular injection also helps to localize the effect.
The point is that you must "prove" the plasmid, adenovirus vector, etc. does not migrate to a remote site. Even as good as electroporation is, it is not 100% intracellular given the IM administration mode. If I were testing this concept, I would use the same mouse model of ischemia, but put a SC and/or IM implanted tumor in a proximal (to the heart) position from where I treated. Then treat the ischemia in the test animals and compare them with untreated controls with tumors. If there is improved blood flow in the treated mice and the tumor growth data is the same, then no neovascular plasmid escaped to cause the tumor to grow faster. As long as the tumor implant is between the treatment site and the heart, that is what you are testing to verify as part of the safety file. It is standard for human or veterinary drugs to test for possible toxic (non-safe) side effects. The FDA knows this based on their collaborations with NIH which also performs preclinical studies with plasmids, adeno vectors, etc.