Current Gene Therapy

In recent years, Genome-Wide Association Studies (GWAS) and next-generation sequencing technologies have been widely used to detect the common genetic variants of diseases. Despite these successes, the majority of the genetic architecture of human complex diseases remains unknown. In the post-genome era, the major challenge is to mine novel disease risks from multi-level omics data using system biology methods, which may expand our knowledge of the causes of genetic disease. Therefore, we (Liang Cheng, and Yang Hu) conducted a Special Issue of Current Gene Therapy about the topic 'human disease system biology'. In this thematic issue, five outstanding works were presented from P.R. China and USA. Cancerlectin plays a key role in the process of tumor cells interacting with each other e.g. cell adhesion, cell growth, tumor cell differentiation, metastasis and cellular infection. With the avalanche of peptide sequences generated in the postgenomic age, it is urgent and challenging to develop an automated method for rapidly and accurately identifying cancerlectins based on their sequences information alone. The review provided the development of a machine learning method in cancerlectin prediction [1]. The authors developed a deep forest-based protein location algorithm relying on sequence information. A random forest network with a multi-layered structure that has a significantly smaller number of parameters was used to identify the subcelluar regions of the protein. It achieved a high accuracy outperforming current state-of-art algorithm given only the protein sequence [2]. System biology methods have been widely used to dissect the mechanisms underpinning human diseases. Here Wang et al. performed an RNA immunoprecipitation (RIP)-seq to profile the EZH2-binding lncRNAs in different tissues including brain, lung, heart, liver, kidney, intestine, spleen, testis, muscle and blood. As a result, Wang et al. identified 1,328 EZH2-binding lncRNAs, among which 470 were shared in at least two tissues while 858 were only detected in single tissue. In addition, to validate those EZH2-binding lncRNAs being previously reported, results uncover numerous novel tissue-specific lncRNAs interacting with EZH2. The findings suggest a critical role of epigenetic regulation by lncRNAs during cell differentiation and maturation [3]. Li et al. explored autophagic activity between normal endometrium and Endometriosis (EMs) lesion endometrium during different menstrual phases and EMs stages. After conducting an observational study on 73 women including 30 healthy individuals and 43 patients with EMs, they observed that the periodicity-losing in EMs and the decreased autophagic activity in ectopic endometrium may exert a potential role in the pathogenesis of EMs. And down-regulated autophagy of ectopic endometrium in secretory phase may be related to the progression of EMs [4] Xu et al. proposed a valid keystone species identification method named Spread Intensity (SI) which try to identify the key potential microbes in gut microbiota associated with adiposity. SI assembled three correlation metrics to calculate the interspecies correlation, applied network deconvolution to remove indirect correlations and used Molecular Ecological Network Analysis (MENA) to construct the co-occurrence network. Then SI combined topological properties of the microbial ecological network and characteristics of the microbial community to identify the key nodes in networks. For evaluating the accuracy of SI, they compared SI algorithm with existing methods by simulated data and got an obvious better performance than the other results. Also, the experimental results in gut microbiota datasets show that SI has an excellent performance in identifying highly correlated species in gut microbiome to adiposity [5]. We wish to end this editorial by thanking Dr. Lung-Ji Chang and Dr. Alfred S. Lewin, the Editor(s) in Chief, as well as Ms. Uroosa Aziz, the Journal Manager. We furthermore, extend our thanks to all peer reviewers for their time and expertise in revising individual contributions.

Lysosomial Storage Disorders (LSDs) are genetic diseases due to a lysosomial dysfunction [1]. LSDs are generally caused by mutations on gene transcribing for a crucial enzyme involved in a metabolic or catabolic biochemical step of a metabolic pathway driving to the accumulation of the not cabolized enzymatic target within the lysosome. Owing to this progressive intralysosomial accumulation lysosomial diseases are characterized by several organ symptoms involving specific or multiple organs [2]. Since this pathogenetic basis of LSDs, they are potential target for gene therapy in order to obtain the single gene induction into some target cells aiming to improve the clinical course of progressive end-organ damage due to continous substrate accumulation [3]. Other possible therapeutic approaches have been reported such as Bone Marrow Transplantation (BMT) or Enzyme Replacement Therapy (ERT) and these therapeutic ways have been reported as able to modify with a various degree the he systemic disease associated with LSDs in some patients. Nevertheless, Central Nervous System (CNS) involvement still appear as a maior therapeutic a major challenge. With regard of treatment of neurologic complications of LSDs cene therapy could be evaluated as a promising future approach for the treatment of CNS disease in order to provide a effective and persistent improvement of the deficient enzyme [4]. Direct intracranial injection of viral gene transfer vectors represents a possible effective therapeutical approach on the basis of promising results reported in some animal models of LSDs such as canine and feline models of lysosomial accumulation diseases. Aim of this mini-thematic issue is to review the state of art of gene therapy in LSDs In the first review, Simonetta et al. [5] reviewed genetics and the role of genetic therapy in Anderson-fabry Disease (AFD). Because of its multisystemic involvement, Fabry’s disease may present a large spectrum of clinical manifestations as acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement (renal insufficiency, proteinuria, left ventricular hypertrophy, strokes) [5-10]. Enzyme replacement therapy with recombinant α-galactosidase A is actually the specific therapy for Fabry’s disease but recently viral gene therapy has recently been addressed with great interest or the last innovative method, that is to say, for delivering recombination enzyme into the main involved tissues and promising results have been reported in animal models. In the second review, Sestito et al. [11] reviewed the role of genetics and genetic therapy in Hunter syndrome. Hunter syndrome is a rare X-linked lysosomal storage disorder due to a mutation in the gene encoding the lysosomal enzyme iduronate-2- sulfatase. The Author reported that In vitro studies firstly aimed at the demonstration that viral vector-mediated IDS gene expression could lead to high levels of enzyme activity in trasduced cells, whereas in vivo studies in which recombinant vectors are directly administered, systematically or by direct injection into the Central Nervous System, also ex vivo gene therapy, consisting of the transplantation of autologous hematopoietic stem cells, modified in vitro, into the animal or patient, indicate future promising results. In the third review, Cachón-González et al., [12] reviewed genetics and gene therapy in GM2 Gangliosidosis. There is no effective treatment beyond palliative care, and while the genetic basis of GM2 gangliosidosis is well established, the molecular and cellular events, from disease-causing mutations and glycosphingolipid storage to disease manifestations, remain to be fully delineated. Several therapeutic approaches have been attempted in patients, including enzymatic augmentation, bone marrow transplantation, enzyme enhancement, and substrate reduction therapy. Animal models of GM2 gangliodidosis have facilitated in-depth evaluation of innovative applications such as gene transfer, which in contrast to other interventions, show great promise.

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