Efficient integration of functional genes is an essential prerequisite for successful gene delivery such as cell transfection, animal transgenesis, and gene therapy. Gene delivery strategies based on viral vectors are currently the most efficient. However, limited cargo capacity, host immune response, and the risk of insertional mutagenesis are limiting factors and of concern. Recently, several groups have used transposon-based approaches to deliver genes to a variety of cells. The piggyBac (pB) transposase in particular has been shown to be well suited for cell transfection and gene therapy approaches because of its flexibility for molecular modification, large cargo capacity, and high transposition activity. However, safety considerations regarding transposase gene insertions into host genomes have rarely been addressed. Here we report our results on engineering helper-independent pB plasmids. The single-plasmid gene delivery system carries both the piggyBac transposase (pBt) expression cassette as well as the transposon cargo flanked by terminal repeat element sequences. Improvements to the helper-independent structure were achieved by developing new plasmids in which the pBt gene is rendered inactive after excision of the transposon from the plasmid. As a consequence, potentially negative effects that may develop by the persistence of an active pBt gene posttransposition are eliminated. The results presented herein demonstrate that our helper-independent plasmids represent an important step in the development of safe and efficient gene delivery methods that should prove valuable in gene therapy and transgenic approaches.
Emerging data show that cardiovascular disease (CVD) continues to be the leading cause of death in women and the annual mortality rate from CVD remains higher in women compared to men. Recent studies demonstrate sex-specific differences in patients presenting with ACS. Comorbidities, especially diabetes, are more common in young women compared with age-matched men who develop acute myocardial infarction (AMI). Women are more likely to have atypical symptoms and nonobstructive coronary disease on angiography. Women are less likely to receive guideline-based therapies. They have higher rates of peri-procedural complications with PCI and are less likely to be referred to cardiac rehabilitation. Awareness of differences in the underlying pathophysiology of coronary disease in women compared to men may lead to improved gender-based diagnostic and treatment modalities. However, until more studies are performed, efforts should be directed toward improving delivery of current, gender-neutral guidelines in women just as in men.
Mechanical complications of acute myocardial infarction are infrequent in the modern era of primary percutaneous coronary intervention, but they are associated with high mortality rates. Papillary muscle rupture with acute severe mitral regurgitation is one such life-threatening complication that requires early detection and urgent surgical intervention. (
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