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Fulltext Genetic and population studies of the blood types and serum factors among Indians and Chinese from Malaya

Steinberg AG, Lai LYC, Vos GH, Singh RB, Lim TW

Am J Hum Genet, 1961 Dec;13:355-71.
PMID: 13916666

The ABO, MN and Rh blood types, and the Hp, Tf, and Gm [Gm (a), Gm (x), Gm(b), and Gm-like] factors were determined for 128 unrelated Indians (parents of families, 63 with two parents tested and two with one parent tested), and 90 unrelated Chinese (parents of 46 families, 44 with two parents tested and two with one parent tested), and for the offspring from these families. The frequencies of the several blood types are presented. They were done primarily to aid in paternity testing. They compare favorably with the findings of previous studies. The allele Hp1 is rare in the Indian population (.09) and relatively infrequent in the Chinese (.29). Unfortunately, the data shed no light on the problem of the inheritance of the phenotype Hp O. Only Tf C was found among the Indians. About four per cent of the Chinese were heterozygous for Tf CD,, all other were Tf CC. The Indians have a high frequency of Gm(a) and of Gm (x), and a low frequency of Gm (b). They appear to have alleles Gma, Gmax, and Gmb in the following frequencies: .535, .234(5), and .230(5), respectively. Three families appear to have a GMxb allele, providing the offspring are not extra-marital. The Chinese appear to have the alleles Gm^ab, Gm^a, and Gm^ax in the following frequencies: .741, .231, and .028, respectively.

Matched MeSH terms: Genetic Therapy*
Current issues in the management of thalassaemia

Rahman Jamal

Malaysian Journal of Child Health, 1998;10(1):1-8.
MyJurnal

The thalassaemias are the commonest single gene disorders amongst the inherited diseases. In Malaysia, there are an estimated 2200 transfusion dependent thalassaemia patients. With a carrier rate of 3-5%, 120-340 new cases of thalassaemia are expected to be born each year. The reference treatments for these patients are regular blood transfusions and iron chelation therapy. With optimal management, these patients are able to survive into the third or fourth decade of life and most importantly avoid the complications related to transfusions and iron overload. The use of desferal locally is still limited to only those who can afford i.e. about 30% of the cases. Treatment for some of the complications such as hepatitis C, diabetes mellitus, growth impairment and pubertal delay, are now available. Curative treatment approaches like bone marrow transplantation have now become standard treatment for eligible cases whilst cord blood transplantation may yet offer hope for those who are without compatible sibling donors. Research on globin gene therapy looks very promising but will probably take some time to deliver. Hb F switching is a very novel idea but so far the results are mainly anecdotal. Finally, the strive for optimal management of thalassaemia must come hand in hand with a prevention programme to achieve a reduction of new cases.

Matched MeSH terms: Genetic Therapy
Analysis of brain tumours suitable for curability via gene therapy in North East Malaysia

Abdullah J, Isa MN

Stereotact Funct Neurosurg, 1999;73(1-4):19-22.
PMID: 10853092

Two hundred primary brain tumours in both adults and children from the year 1990 to 1998 presenting for treatment to the Neurosurgical Division of the Hospital of the University of Sciences Malaysia were studied retrospectively. Volumes of tumours were taken from CT scans with contrast using two formulas and divided into 4 groups: (1) less than 20 cm(3), (2) 20-50 cm(3), (3) 50-100 cm(3) (4) larger than 100 cm(3). The majority of the brain tumours were in the volume range of 50-100 cm(3), and are thus potentially curable with retroviral gene therapy.

Matched MeSH terms: Genetic Therapy*
Fulltext Cell targeting in anti-cancer gene therapy

Lila MA, Siew JS, Zakaria H, Saad SM, Ni LS, Abdullah JM

Malays J Med Sci, 2004 Jan;11(1):9-23.
PMID: 22977356 MyJurnal

Gene therapy is a promising approach towards cancer treatment. The main aim of the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and preserving others. However, its application has been hindered by many factors including poor cellular uptake, non-specific cell targeting and undesirable interferences with other genes or gene products. A variety of strategies exist to improve cellular uptake efficiency of gene-based therapies. This paper highlights advancements in gene therapy research and its application in relation to anti-cancer treatment.

Matched MeSH terms: Genetic Therapy
Induced expression of the antimicrobial peptide melittin inhibits experimental infection by Mycoplasma gallisepticum in chickens

Lazarev VN, Stipkovits L, Biro J, Miklodi D, Shkarupeta MM, Titova GA, et al.

Microbes Infect., 2004 May;6(6):536-41.
PMID: 15158186

The in vivo action of the antimicrobial peptide melittin, expressed from a recombinant plasmid vector, on chickens experimentally infected with Mycoplasma gallisepticum was studied. The plasmid vector pBI/mel2/rtTA includes the melittin gene under the control of an inducible tetracycline-dependent human cytomegalovirus promoter and the gene coding for the trans-activation protein rtTA. Aerosol administration of the vector, followed by infecting the chickens with M. gallisepticum 1226, is shown to inhibit development of infection. The inhibitory action was confirmed by a complex of clinical, pathomorphological, histological and serological studies, and also by comparing the M. gallisepticum reisolation frequency from the respiratory tract and internal organs. The data suggest that plasmid vectors expressing genes of antimicrobial peptides can be considered as potential agents for the prevention and treatment of mycoplasma infections in poultry farming.

Matched MeSH terms: Genetic Therapy/veterinary*
Effect of induced expression of an antimicrobial peptide melittin on Chlamydia trachomatis and Mycoplasma hominis infections in vivo

Lazarev VN, Shkarupeta MM, Titova GA, Kostrjukova ES, Akopian TA, Govorun VM

Biochem Biophys Res Commun, 2005 Dec 16;338(2):946-50.
PMID: 16246304

A plasmid construct was designed in which the gene of antimicrobial peptide melittin is controlled by the tetracycline-responsive promoter of human cytomegalovirus, aided by a constitutively expressed trans-activator protein gene. Its vaginal administration and induction of melittin gene transcription with doxycycline markedly suppressed subsequent genital tract infection of mice by Mycoplasma hominis and Chlamydia trachomatis. At least half of the melittin-protected animals proved free of either pathogen within 3-4 weeks. Recombinant plasmids expressing genes of antimicrobial peptides hold much promise as agents for prevention and control of urogenital latent infections.

Matched MeSH terms: Genetic Therapy/methods
Nuclear targeting of viral and non-viral DNA

Chowdhury EH

Expert Opin Drug Deliv, 2009 Jul;6(7):697-703.
PMID: 19552613 DOI: 10.1517/17425240903025744

The nuclear envelope presents a major barrier to transgene delivery and expression using a non-viral vector. Virus is capable of overcoming the barrier to deliver their genetic materials efficiently into the nucleus by virtue of the specialized protein components with the unique amino acid sequences recognizing cellular nuclear transport machinery. However, considering the safety issues in the clinical gene therapy for treating critical human diseases, non-viral systems are highly promising compared with their viral counterparts. This review summarizes the progress on exploring the nuclear traffic mechanisms for the prominent viral vectors and the technological innovations for the nuclear delivery of non-viral DNA by mimicking those natural processes evolved for the viruses as well as for many cellular proteins.

Matched MeSH terms: Genetic Therapy
Strategies for tumor-directed delivery of siRNA

Chowdhury EH

Expert Opin Drug Deliv, 2011 Mar;8(3):389-401.
PMID: 21314230 DOI: 10.1517/17425247.2011.554817

Current treatment of malignant tumors relies predominantly on chemotherapy delivering a single antineoplastic drug or a combination of two or more drugs intravenously. Problems with such treatments can include the killing of healthy cells, adverse side effects and chemoresistance. As cancer basically results from different types of mutation leading to the overexpression or suppression of the signaling cascades responsible for cancer cell survival and proliferation, tailor-made approaches capable of interfering precisely with those pathways are the potential revolutionary tools that could pave the way for highly effective cancer therapy.

Matched MeSH terms: Genetic Therapy/methods*
Fulltext Spider venom peptides for gene therapy of Chlamydia infection

Lazarev VN, Polina NF, Shkarupeta MM, Kostrjukova ES, Vassilevski AA, Kozlov SA, et al.

Antimicrob Agents Chemother, 2011 Nov;55(11):5367-9.
PMID: 21876050 DOI: 10.1128/AAC.00449-11

Spider venoms are vast natural pharmacopoeias selected by evolution. The venom of the ant spider Lachesana tarabaevi contains a wide variety of antimicrobial peptides. We tested six of them (latarcins 1, 2a, 3a, 4b, 5, and cytoinsectotoxin 1a) for their ability to suppress Chlamydia trachomatis infection. HEK293 cells were transfected with plasmid vectors harboring the genes of the selected peptides. Controlled expression of the transgenes led to a significant decrease of C. trachomatis viability inside the infected cells.

Matched MeSH terms: Genetic Therapy/methods
Fulltext Engineering an L-cell line that expresses insulin under the control of the glucagon-like peptide-1 promoter for diabetes treatment

Rasouli M, Ahmad Z, Omar AR, Allaudin ZN

BMC Biotechnol, 2011 Nov 03;11:99.
PMID: 22047106 DOI: 10.1186/1472-6750-11-99

BACKGROUND: Diabetes mellitus is a complicated disease with a pathophysiology that includes hyperinsulinemia, hyperglycemia and other metabolic impairments leading to many clinical complications. It is necessary to develop appropriate treatments to manage the disease and reduce possible acute and chronic side effects. The advent of gene therapy has generated excitement in the medical world for the possible application of gene therapy in the treatment of diabetes. The glucagon-like peptide-1 (GLP-1) promoter, which is recognised by gut L-cells, is an appealing candidate for gene therapy purposes. The specific properties of L-cells suggest that L-cells and the GLP-1 promoter would be useful for diabetes therapy approaches.
RESULTS: In this study, L-cells were isolated from a primary intestinal cell line to create suitable target cells for insulin expression studies. The isolated cells displayed L-cell properties and were therefore used as an L-cell surrogate. Next, the isolated L-cells were transfected with the recombinant plasmid consisting of an insulin gene located downstream of the GLP-1 promoter. The secretion tests revealed that an increase in glucose concentration from 5 mM to 25 mM induced insulin gene expression in the L-cells by 2.7-fold. Furthermore, L-cells quickly responded to the glucose stimulation; the amount of insulin protein increased 2-fold in the first 30 minutes and then reached a plateau after 90 minutes.
CONCLUSION: Our data showed that L-cells efficiently produced the mature insulin protein. In addition, the insulin protein secretion was positively regulated with glucose induction. In conclusion, GLP-1 promoter and L-cell could be potential candidates for diabetes gene therapy agents.

Matched MeSH terms: Genetic Therapy/methods
Fulltext Adenoviral based gene therapy for cancer in human and animals: a review

Shin, Tan Seok, Zeenathul Nazariah Allaudin, Mohd. Azmi Mohd. Lila

Pertanika Journal of Science & Technology, 2011;19(1):129-140.
MyJurnal

Adenovirus vector is the most common used vector in clinical gene therapy. The development of adenovirus from the first generation until the helper-dependent adenovirus vector has greatly reduced toxicity and immunogenicity. The helper-dependent adenovirus can also prolong transgene expression. Tissue- or disease-specific approach has been used to improve the specificity of adenoviral vector for cancer gene therapy. This review summarizes some adenoviral gene therapy and targeting approaches available for human cancer as well as animal cancer.

Matched MeSH terms: Genetic Therapy
Fulltext Induced pluripotent stem cells in research and therapy

Teoh HK, Cheong SK

Malays J Pathol, 2012 Jun;34(1):1-13.
PMID: 22870592 MyJurnal

Induced pluripotent stem cells (iPSC) are derived from human somatic cells through ectopic expression of transcription factors. This landmark discovery has been considered as a major development towards patient-specific iPSC for various biomedical applications. Unlimited self renewal capacity, pluripotency and ease of accessibility to donor tissues contribute to the versatility of iPSC. The therapeutic potential of iPSC in regenerative medicine, cell-based therapy, disease modelling and drug discovery is indeed very promising. Continuous progress in iPSC technology provides clearer understanding of disease pathogenesis and ultimately new optimism in developing treatment or cure for human diseases.

Matched MeSH terms: Genetic Therapy
Fulltext Scaling-up recombinant plasmid DNA for clinical trial: current concern, solution and status

Ismail R, Allaudin ZN, Lila MA

Vaccine, 2012 Sep 7;30(41):5914-20.
PMID: 22406276 DOI: 10.1016/j.vaccine.2012.02.061

Gene therapy and vaccines are rapidly developing field in which recombinant nucleic acids are introduced in mammalian cells for enhancement, restoration, initiation or silencing biochemical function. Beside simplicity in manipulation and rapid manufacture process, plasmid DNA-based vaccines have inherent features that make them promising vaccine candidates in a variety of diseases. This present review focuses on the safety concern of the genetic elements of plasmid such as propagation and expression units as well as their host genome for the production of recombinant plasmid DNA. The highlighted issues will be beneficial in characterizing and manufacturing plasmid DNA for save clinical use. Manipulation of regulatory units of plasmid will have impact towards addressing the safety concerns raised in human vaccine applications. The gene revolution with plasmid DNA by alteration of their plasmid and production host genetics will be promising for safe delivery and obtaining efficient outcomes.

Matched MeSH terms: Genetic Therapy/methods
Fulltext Production of Lentivirus carrying green fluorescent protein with different promoters for in vitro gene transfer

Siew, Ching Ngai, Ramasamy, Rajesh, Syahril Abdullah

Pertanika Journal of Science & Technology, 2012;20(2):269-281.
MyJurnal

Many diseases are potential targets for gene therapy using either non-viral or viral vectors. Unlike nonviralmethods, viral vectors, such as lentiviruses, have the ability to integrate into the host chromosome,which can lead to long-term transgene expression. Lentiviruses have advantages over other types ofviruses due to their capacity to transduce non-dividing cells. An optimized generation of lentivirusescarrying green fluorescent protein (GFP) reporter gene driven by either UbC (LV/UbC/GFP) orCMV (LV/CMV/GFP) promoter is described in this paper. The lentiviruses were produced by cotransfectinglentiviral expression constructs and packaging mix into 293FT lentivirus producer cell lines.Lipofectamine was highly efficient in transfecting the cells compared to Transfast and Polyethyleneimine(PEI). Following cell transfection, syncytia were clearly visible at day 2. Lentiviruses were harvestedat days 1, 2 and 3 post-transfection. The highest transduction efficiency was read from LV/CMV/GFPharvested at day 2 post-transfection and LV/UbC/GFP harvested at day 3 post-transfection. Finally,the GFP expression in COS-7 cells was determined at day 2 and day 14 post-transduction for transientand stable GFP expression. It was found that the GFP expression declined overtime. However, thetransduction efficiency and duration of the transgene expression in COS-7 cells transduced with LV/CMV/GFP were higher compared to LV/UbC/GFP. In conclusion, we have successfully produced lentivirusescarrying GFP with different promoters and shown that the viruses were able to infect COS-7 cells atdifferent efficiencies. Meanwhile, the generation of the active lentiviruses will allow us to proceed to the subsequent analysis of the effect of regulatory elements in future study.

Matched MeSH terms: Genetic Therapy
Fulltext Bcl-xL silencing induces alterations in hsa-miR-608 expression and subsequent cell death in A549 and SK-LU1 human lung adenocarcinoma cells

Othman N, In LL, Harikrishna JA, Hasima N

PLoS One, 2013;8(12):e81735.
PMID: 24339958 DOI: 10.1371/journal.pone.0081735

Bcl-xL is an anti-apoptotic protein that is frequently found to be overexpressed in non-small cell lung cancer leading to an inhibition of apoptosis and poor prognosis. Recently, the role of miRNAs in regulating apoptosis and cell survival during tumorigenesis has become evident, with cancer cells showing perturbed expression of various miRNAs. In this study, we utilized miRNA microarrays to determine if miRNA dysregulation in bcl-xL silenced lung adenocarcinoma cells could be involved in regulating cell death. Short interfering RNA-based transfection of A549 and SK-LU1 lung adenocarcinoma cells was successful in inducing a reduction in bcl-xL expression levels, resulting in a decrease in cell viability. A total of 10 miRNAs were found to be significantly differentially expressed when compared between siRNA-transfected and non-transfected cells including hsa-miR-181a, hsa-miR-769-5p, hsa-miR-361-5p, hsa-miR-1304 and hsa-miR-608. When overexpression studies on hsa-miR-608 was performed via transfection of miRNA mimics, cell death was found to be induced in A549 and SK-LU1 cells in comparison to untreated cells. This effect was reversed when knockdown studies involving anti-sense inhibitors were introduced. Combination of siRNA based silencing of bcl-xL (siBcl-xL) followed by anti-sense inhibitor transfection led to a decrease in the apoptotic population of A549 and SK-LU1 cells in comparison to cells only treated with siBcl-xL, illustrating the connection between bcl-xL, hsa-miR-608 and cell death. Gene target prediction analysis implicated the PI3K/AKT, WNT, TGF-β, and ERK signaling pathways as targets of bcl-xL induced miRNA alterations. We have demonstrated that bcl-xL silencing in A549 and SK-LU1 cells leads to the occurrence of cell death through the dysregulation of specific miRNAs. This study also provides a platform for anti-sense gene therapy whereby miRNA expression can be exploited to increase the apoptotic properties in lung adenocarcinoma cells.

Matched MeSH terms: Genetic Therapy
Fulltext Soluble Flt-1 gene delivery in acute myeloid leukemic cells mediating a nonviral gene carrier

Amini R, Azizi Jalilian F, Veerakumarasivam A, Abdullah S, Abdulamir AS, Nadali F, et al.

Biomed Res Int, 2013;2013:752603.
PMID: 23509773 DOI: 10.1155/2013/752603

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in angiogenesis-mediated progression of acute myeloid leukemia (AML). Studies have reported the role of soluble form of fms-like tyrosine kinase (sFlT-1) delivery as an antitumor agent by inhibiting VEGF. This study investigates the outcome of delivery of a VEGF165 antagonist, soluble vascular endothelial growth factor receptor, namely sFLT-1, mediating lipofectamine 2000 in acute myeloid leukemic cells. A recombinant plasmid expressing sFLT-1 was constructed and transfected into the K562 and HL60 cells using lipofectamine 2000 transfection reagent. sFLT-1 expression/secretion in pVAX-sFLT-1 transfected cells was verified by RT-PCR and western blot. MTS assay was carried out to evaluate the effect of sFLT-1 on human umbilical vein endothelial cells and K562 and HL60 cells in vitro. Treatment with pVAX-sFLT-1 showed no association between sFLT-1 and proliferation of infected K562 and HL60 cells, while it demonstrated a significant inhibitory impact on the proliferation of HUVECs. The results of the current study imply that the combination of nonviral gene carrier and sFLT-1 possesses the potential to provide efficient tool for the antiangiogenic gene therapy of AML.

Matched MeSH terms: Genetic Therapy
Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy

Bakhtiar A, Sayyad M, Rosli R, Maruyama A, Chowdhury EH

Curr Gene Ther, 2014;14(4):247-57.
PMID: 25039616

Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

Matched MeSH terms: Genetic Therapy/methods*
Fulltext Gene technology for papaya ringspot virus disease management

Azad MA, Amin L, Sidik NM

ScientificWorldJournal, 2014;2014:768038.
PMID: 24757435 DOI: 10.1155/2014/768038

Papaya (Carica papaya) is severely damaged by the papaya ringspot virus (PRSV). This review focuses on the development of PRSV resistant transgenic papaya through gene technology. The genetic diversity of PRSV depends upon geographical distribution and the influence of PRSV disease management on a sequence of PRSV isolates. The concept of pathogen-derived resistance has been employed for the development of transgenic papaya, using a coat protein-mediated, RNA-silencing mechanism and replicase gene-mediated transformation for effective PRSV disease management. The development of PRSV-resistant papaya via post-transcriptional gene silencing is a promising technology for PRSV disease management. PRSV-resistant transgenic papaya is environmentally safe and has no harmful effects on human health. Recent studies have revealed that the success of adoption of transgenic papaya depends upon the application, it being a commercially viable product, bio-safety regulatory issues, trade regulations, and the wider social acceptance of the technology. This review discusses the genome and the genetic diversity of PRSV, host range determinants, molecular diagnosis, disease management strategies, the development of transgenic papaya, environmental issues, issues in the adoption of transgenic papaya, and future directions for research.

Matched MeSH terms: Genetic Therapy*
Gene therapy in dentistry: tool of genetic engineering. Revisited

Gupta K, Singh S, Garg KN

Arch Oral Biol, 2015 Mar;60(3):439-46.
PMID: 25540850 DOI: 10.1016/j.archoralbio.2014.11.018

Advances in biotechnology have brought gene therapy to the forefront of medical research. The concept of transferring genes to tissues for clinical applications has been discussed nearly half a century, but the ability to manipulate genetic material via recombinant DNA technology has brought this goal to reality. The feasibility of gene transfer was first demonstrated using tumour viruses. This led to development of viral and nonviral methods for the genetic modification of somatic cells. Applications of gene therapy to dental and oral problems illustrate the potential impact of this technology on dentistry. Preclinical trial results regarding the same have been very promising. In this review we will discuss methods, vectors involved, clinical implication in dentistry and scientific issues associated with gene therapy.

Matched MeSH terms: Genetic Therapy*
MicroRNA-based therapy and breast cancer: A comprehensive review of novel therapeutic strategies from diagnosis to treatment

Kaboli PJ, Rahmat A, Ismail P, Ling KH

Pharmacol Res, 2015 Jul;97:104-21.
PMID: 25958353 DOI: 10.1016/j.phrs.2015.04.015

MicroRNAs (miRNA) are 21-23 nucleotide molecules not translated into proteins that bind and target the 3' untranslated regions of mRNA. These characteristics make them a possible tool for inhibiting protein translation. Different cellular pathways involved in cancer development, such as cellular proliferation, apoptosis, and migration, are regulated by miRNAs. The objective of this review is to discuss various miRNAs involved in breast cancer in detail as well as different therapeutic strategies from the clinic to industry. A comprehensive discussion is provided on various miRNAs involved in breast cancer development, progression, and metastasis as well as the roles, targets, and related therapeutic strategies of different miRNAs associated with breast cancer. miRNAs known to be clinically useful for the diagnosis and prognosis of breast cancer are also discussed. Different strategies and challenges, including nucleic acid-based (miRNA mimics, antagomiRs, and miRNA sponges) and drug-based (drug resistance, drugs/miRNA interaction, nanodelivery, and sensing systems) approaches to suppress specific oncogenes and/or activate target tumor suppressors are discussed. In contrast to other articles written on the same topic, this review focuses on the therapeutic and clinical value of miRNAs as well as their corresponding targets in order to explore how these strategies can overcome breast cancer, which is the second most frequent type of cancer worldwide. This review focuses on promising and validated miRNAs involved in breast cancer. In particular, two miRNAs, miR-21 and miR-34, are discussed as the most promising targets for RNA-based therapy in non-invasive and invasive breast cancer, respectively. Finally, relevant and commercialized therapeutic strategies are highlighted.

Matched MeSH terms: Genetic Therapy/methods*

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