A key end goal of gene delivery research is to develop clinically-relevant vectors that can be used to combat elusive diseases such as AIDS. Despite promising engineering strategies, efficiency and ultimately gene modulation efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo barriers that have resulted in sub-viral performance. In this perspective, we concentrate on the gene delivery barriers associated with the two most common classes of nonviral vectors, cationic-based lipids and polymers. We present the existing delivery barriers and summarize current vector-specific strategies to overcome said barriers.
Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly (beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.
Improvements to bacterial vectors have resulted in non-viral gene therapy vehicles that are easily prepared and can achieve high levels of transfection efficacy. However, these vectors are plagued by potential cytotoxicity and immunogenicity, prompting means of attenuation to reduce unwanted biological outcomes while maintaining transfection efficiency. In this study, listeriolysin O (LLO) producing Escherichia coli BL21(DE3) strains were pre-treated with polymyxin B (PLB), a pore-forming antibiotic, and tested as a delivery vector for gene transfer to a murine RAW264.7 macrophage cell line using a 96-well high-throughput assay. PLB treatment resulted in statistically significant higher levels of gene delivery and lower cytotoxicity. The results suggest a fine balance between bacterial cellular damage, heightened gene and protein release, and increased mammalian cell gene delivery. Overall, the approach presented provides a simple and effective way to enhance bacterial gene delivery while simultaneously reducing unwanted outcomes as a function of using a biological vector.
Bactofection offers a gene delivery option particularly useful in the context of immune modulation. The bacterial host naturally attracts recognition and cellular uptake by antigen presenting cells (APCs) as the initial step in triggering an immune response. Moreover, depending on the bacterial vector, molecular biology tools are available to influence and/or overcome additional steps and barriers to effective antigen presentation. In this work, molecular engineering was applied using Escherichia coli as a bactofection vector. In particular, the bacteriophage ΦX174 lysis E (LyE) gene was designed for variable expression across strains containing different levels of lysteriolysin O (LLO). The objective was to generate a bacterial vector with improved attenuation and delivery characteristics. The resulting strains exhibited enhanced gene and protein release and inducible cellular death. In addition, the new vectors demonstrated improved gene delivery and cytotoxicity profiles to RAW264.7 macrophage APCs.
is described in Ayurveda, having many clinical features similar to different types of anemia as mentioned in Modern text."Pandu" means a white colour mixed with yellowish Tinge as mentioned in Amarakosha . According to Charaka Samhita-In this disease the skin ofpatient isdiscoloured as Pandu or like haridra or greenish tinge. According to Sushruta Samhita in all types of Pandu body of the patient is more Pandu (shwetarakta or shweta pita).So it is named as Pandu. In Ayurveda Charaka has mentioned it as Rasavaha Srotodushti. Susruta has mentioned it as RaktavahaSrotodushti. A prominent diagnostic feature of Pandu roga is the pallor on the skin which occurs due to the quantitative and qualitative deficiency of raktudhatu(1).Besides the various etiological factors Aaharajahetu and ViharajaHetu plays an important role . In this modern era, people are unaware of their day-to-day life style. There is a drastic change in their livings. And this has made their life more complicated and which are leading for occurrence for many disease. Factors affecting manifestation of disease are change in the life style, high population, socio economic cause, stress, uncontrolled diet, addictions and lot more. According to Ayurveda, the best treatment for all the disease is nidanparivarjan means to avoid all the causative factors. So in order to make people disease free and to make people aware, review study of dincharya as nidanparivarjan of panduvyadhi has been presented in this paper.
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