Displaying publications 1 - 20 of 59 in total

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  1. 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*
  2. Fulltext Fish gelatin nanoparticles and their food applications: A review
    Akbar, I., Jaswir, I., Jamal, P., Octavianti, F.
    International Food Research Journal, 2017;24(101):0-0.
    MyJurnal
    Considerable attention has been directed to nanoparticles based on gelatin biopolymer due to its numerous available active group sites for attaching target molecules and acting as a drug or nutraceutical delivery system aiming to improve the therapeutic effects and also to reduce the side effects of formulated drugs as gelatin is a natural biodegradable biocompatible polymer, nontoxic, readily available, cheap and is used in parental formulations. With mammalian gelatin (pig and cow) as the major source of gelatin production, alternatives are required due to sociocultural and health concerns to maintain halal status. This paper aims at reviewing fish skin gelatin from warm water species which can provide a potential alternative source of gelatin with almost the same rheological properties as mammalian gelatin and is a beneficial way to use fish waste such as skin, bones and fin which is generally discarded. The study also entails a lot of research being done in the field of nanoencapsulation of gelatin with various nutraceuticals as well as drug and gene therapy. There is an especially increasing interest in encapsulating biopeptides within gelatin nanoparticles in the functional food industry due to their role in preventing or delaying the onset of various diseases, food fortification, improvement of food quality, increase in shelf life, targeted peptide delivery and hence can be used as additives in food products. This review also attempts to provide an overview of the application of gelatin nanoparticles in nanoencapsulation in the food industry.
    Matched MeSH terms: Genetic Therapy
  3. Insights and future directions of potential genetic therapy for Apert syndrome: A systematic review
    Al-Namnam NM, Jayash SN, Hariri F, Rahman ZAA, Alshawsh MA
    Gene Ther, 2021 Nov;28(10-11):620-633.
    PMID: 33619359 DOI: 10.1038/s41434-021-00238-w
    Apert syndrome is a genetic disorder characterised by craniosynostosis and structural discrepancy of the craniofacial region as well as the hands and feet. This condition is closely linked with fibroblast growth factor receptor-2 (FGFR2) gene mutations. Gene therapies are progressively being tested in advanced clinical trials, leading to a rise of its potential clinical indications. In recent years, research has made great progress in the gene therapy of craniosynostosis syndromes and several studies have investigated its influences in preventing/diminishing the complications of Apert syndrome. This article reviewed and exhibited different techniques of gene therapy and their influences in Apert syndrome progression. A systematic search was executed using electronic bibliographic databases including PubMed, EMBASE, ScienceDirect, SciFinder and Web of Science for all studies of gene therapy for Apert syndrome. The primary outcomes measurements vary from protein to gene expressions. According to the findings of included studies, we conclude that the gene therapy using FGF in Apert syndrome was critical in the regulation of suture fusion and patency, occurred via alterations in cellular proliferation. The superior outcome could be brought by biological therapies targeting the FGF/FGFR signalling. More studies in molecular genetics in Apert syndrome are recommended. This study reviews the current literature and provides insights to future possibilities of genetic therapy as intervention in Apert syndrome.
    Matched MeSH terms: Genetic Therapy
  4. Silencing of transgene expression in mammalian cells by DNA methylation and histone modifications in gene therapy perspective
    Alhaji SY, Ngai SC, Abdullah S
    Biotechnol Genet Eng Rev, 2019 Apr;35(1):1-25.
    PMID: 30514178 DOI: 10.1080/02648725.2018.1551594
    DNA methylation and histone modifications are vital in maintaining genomic stability and modulating cellular functions in mammalian cells. These two epigenetic modifications are the most common gene regulatory systems known to spatially control gene expression. Transgene silencing by these two mechanisms is a major challenge to achieving effective gene therapy for many genetic conditions. The implications of transgene silencing caused by epigenetic modifications have been extensively studied and reported in numerous gene delivery studies. This review highlights instances of transgene silencing by DNA methylation and histone modification with specific focus on the role of these two epigenetic effects on the repression of transgene expression in mammalian cells from integrative and non-integrative based gene delivery systems in the context of gene therapy. It also discusses the prospects of achieving an effective and sustained transgene expression for future gene therapy applications.
    Matched MeSH terms: Genetic Therapy
  5. A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts
    Amini E, Rezaei M, Mohamed Ibrahim N, Golpich M, Ghasemi R, Mohamed Z, et al.
    Mol Neurobiol, 2015 Aug;52(1):492-513.
    PMID: 25195699 DOI: 10.1007/s12035-014-8876-5
    Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.
    Matched MeSH terms: Genetic Therapy
  6. 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
  7. Fulltext Targeting Cell Adhesion Molecules via Carbonate Apatite-Mediated Delivery of Specific siRNAs to Breast Cancer Cells In Vitro and In Vivo
    Ashaie MA, Islam RA, Kamaruzman NI, Ibnat N, Tha KK, Chowdhury EH
    Pharmaceutics, 2019 Jul 02;11(7).
    PMID: 31269666 DOI: 10.3390/pharmaceutics11070309
    While several treatment strategies are applied to cure breast cancer, it still remains one of the leading causes of female deaths worldwide. Since chemotherapeutic drugs have severe side effects and are responsible for development of drug resistance in cancer cells, gene therapy is now considered as one of the promising options to address the current treatment limitations. Identification of the over-expressed genes accounting for constitutive activation of certain pathways, and their subsequent knockdown with specific small interfering RNAs (siRNAs), could be a powerful tool in inhibiting proliferation and survival of cancer cells. In this study, we delivered siRNAs against mRNA transcripts of over-regulated cell adhesion molecules such as catenin alpha 1 (CTNNA1), catenin beta 1 (CTNNB1), talin-1 (TLN1), vinculin (VCL), paxillin (PXN), and actinin-1 (ACTN1) in human (MCF-7 and MDA-MB-231) and murine (4T1) cell lines as well as in the murine female Balb/c mice model. In order to overcome the barriers of cell permeability and nuclease-mediated degradation, the pH-sensitive carbonate apatite (CA) nanocarrier was used as a delivery vehicle. While targeting CTNNA1, CTNNB1, TLN1, VCL, PXN, and ACTN1 resulted in a reduction of cell viability in MCF-7 and MDA-MB-231 cells, delivery of all these siRNAs via carbonate apatite (CA) nanoparticles successfully reduced the cell viability in 4T1 cells. In 4T1 cells, delivery of CTNNA1, CTNNB1, TLN1, VCL, PXN, and ACTN1 siRNAs with CA caused significant reduction in phosphorylated and total AKT levels. Furthermore, reduced band intensity was observed for phosphorylated and total MAPK upon transfection of 4T1 cells with CTNNA1, CTNNB1, and VCL siRNAs. Intravenous delivery of CTNNA1 siRNA with CA nanoparticles significantly reduced tumor volume in the initial phase of the study, while siRNAs targeting CTNNB1, TLN1, VCL, PXN, and ACTN1 genes significantly decreased the tumor burden at all time points. The tumor weights at the end of the treatments were also notably smaller compared to CA. This successfully demonstrates that targeting these dysregulated genes via RNAi and by using a suitable delivery vehicle such as CA could serve as a promising therapeutic treatment modality for breast cancers.
    Matched MeSH terms: Genetic Therapy
  8. 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*
  9. 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*
  10. Parkinson's disease: Cause factors, measurable indicators, and early diagnosis
    Bhat S, Acharya UR, Hagiwara Y, Dadmehr N, Adeli H
    Comput Biol Med, 2018 11 01;102:234-241.
    PMID: 30253869 DOI: 10.1016/j.compbiomed.2018.09.008
    Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system caused due to the loss of dopaminergic neurons. It is classified under movement disorder as patients with PD present with tremor, rigidity, postural changes, and a decrease in spontaneous movements. Comorbidities including anxiety, depression, fatigue, and sleep disorders are observed prior to the diagnosis of PD. Gene mutations, exposure to toxic substances, and aging are considered as the causative factors of PD even though its genesis is unknown. This paper reviews PD etiologies, progression, and in particular measurable indicators of PD such as neuroimaging and electrophysiology modalities. In addition to gene therapy, neuroprotective, pharmacological, and neural transplantation treatments, researchers are actively aiming at identifying biological markers of PD with the goal of early diagnosis. Neuroimaging modalities used together with advanced machine learning techniques offer a promising path for the early detection and intervention in PD patients.
    Matched MeSH terms: Genetic Therapy
  11. Fulltext Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study
    Bong IP, Ng CC, Fakiruddin SK, Lim MN, Zakaria Z
    Bosn J Basic Med Sci, 2016 Nov 10;16(4):268-275.
    PMID: 27754828 DOI: 10.17305/bjbms.2016.1568
    Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.
    Matched MeSH terms: Genetic Therapy
  12. Fulltext Current therapies and targets for type 2 diabetes mellitus
    Chellappan DK, Yap WS, Bt Ahmad Suhaimi NA, Gupta G, Dua K
    Panminerva Med, 2018 Sep;60(3):117-131.
    PMID: 29696964 DOI: 10.23736/S0031-0808.18.03455-9
    The prevalence of type 2 diabetes mellitus (T2DM) has been increasing at an alarming rate. With an increased understanding of the pathophysiology and pathogenesis of T2DM, various new therapeutic options have been developed to target different key defects in T2DM. Incremental innovations of existing therapies either through unprecedented drug combinations, modified drug molecules, or improved delivery systems are capable to nullify some of the undesirable side effects of traditional therapies as well as to enhance effectiveness. The existing administration routes include inhalation, nasal, buccal, parenteral and oral. Newer drug targets such as protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), sirtuin (SIRT), and others are novel approaches that act via different mechanisms and possibly treating T2DM of distinct variations and aetiologies. Other therapies such as endobarrier, gene therapy, and stem cell technology utilize advanced techniques to treat T2DM, and the potential of these therapies are still being explored. Gene therapy is plausible to fix the underlying pathology of T2DM instead of using traditional reactive treatments, especially with the debut of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein9 (CRISPR-Cas9) gene editing tool. Molecular targets in T2DM are also being extensively studied as it could target the defects at the molecular level. Furthermore, antibody therapies and vaccinations are also being developed against T2DM; but the ongoing clinical trials are relatively lesser and the developmental progress is slower. Although, there are many therapies designed to cure T2DM, each of them has their own advantages and disadvantages. The preference for the treatment plan usually depends on the health status of the patient and the treatment goal. Therefore, an ideal treatment should take patient's compliance, efficacy, potency, bioavailability, and other pharmacological and non-pharmacological properties into account.
    Matched MeSH terms: Genetic Therapy
  13. Fulltext Gene therapy and type 1 diabetes mellitus
    Chellappan DK, Sivam NS, Teoh KX, Leong WP, Fui TZ, Chooi K, et al.
    Biomed Pharmacother, 2018 Dec;108:1188-1200.
    PMID: 30372820 DOI: 10.1016/j.biopha.2018.09.138
    BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet β cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors.

    METHODS: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review.

    FINDINGS: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.

    Matched MeSH terms: Genetic Therapy*
  14. 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*
  15. 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
  16. Gene Therapy for Duchenne Muscular Dystrophy: Unlocking the Opportunities in Countries in the Middle East and Beyond
    Elbashir H, Fathalla W, Mundada V, Iqbal M, Al Tawari AA, Chandratre S, et al.
    J Neuromuscul Dis, 2022;9(6):787-801.
    PMID: 36245386 DOI: 10.3233/JND-221528
    BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder which leads to progressive muscle degeneration and weakness. Most patients die from cardiac or respiratory failure. Gene transfer therapy offers a promising approach to treating this disorder.

    OBJECTIVE: Given the genetic disease burden, family size, and the high consanguinity rates in the Middle East, our objective is to address current practices and challenges of DMD patient care within two countries in this region, namely the United Arab Emirates and Kuwait, and to outline readiness for gene therapy.

    METHODS: An expert panel meeting was held to discuss the DMD patient journey, disease awareness, current management of DMD, challenges faced and recommendations for improvement. Opportunities and challenges for gene therapy in both countries were also deliberated. A pre-meeting survey was conducted, and the results were used to guide the discussion during the meeting.

    RESULTS: DMD awareness is poor resulting in a delay in referral and diagnosis of patients. Awareness and education initiatives, along with an interconnected referral system could improve early diagnosis. Genetic testing is available in both countries although coverage varies. Corticosteroid therapy is the standard of care however there is often a delay in treatment initiation. Patients with DMD should be diagnosed and managed by a multi-disciplinary team in centers of excellence for neuromuscular disorders. Key success factors to support the introduction of gene therapy include education and training, timely and accessible genetic testing and resolution of reimbursement and cost issues.

    CONCLUSION: There are many challenges facing the management of DMD patients in the United Arab Emirates and Kuwait and most likely other countries within the Middle East. Successful introduction of gene therapy to treat DMD will require careful planning, education, capacity building and prioritization of core initiatives.

    Matched MeSH terms: Genetic Therapy/methods
  17. 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*
  18. Fulltext Gene Therapy Targeting p53 and KRAS for Colorectal Cancer Treatment: A Myth or the Way Forward?
    Hasbullah HH, Musa M
    Int J Mol Sci, 2021 Nov 03;22(21).
    PMID: 34769370 DOI: 10.3390/ijms222111941
    Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and is responsible as one of the main causes of mortality in both men and women. Despite massive efforts to raise public awareness on early screening and significant advancements in the treatment for CRC, the majority of cases are still being diagnosed at the advanced stage. This contributes to low survivability due to this cancer. CRC patients present various genetic changes and epigenetic modifications. The most common genetic alterations associated with CRC are p53 and KRAS mutations. Gene therapy targeting defect genes such as TP53 (tumor suppressor gene encodes for p53) and KRAS (oncogene) in CRC potentially serves as an alternative treatment avenue for the disease in addition to the standard therapy. For the last decade, significant developments have been seen in gene therapy for translational purposes in treating various cancers. This includes the development of vectors as delivery vehicles. Despite the optimism revolving around targeted gene therapy for cancer treatment, it also has various limitations, such as a lack of availability of related technology, high cost of the involved procedures, and ethical issues. This article will provide a review on the potentials and challenges of gene therapy targeting p53 and KRAS for the treatment of CRC.
    Matched MeSH terms: Genetic Therapy/methods*
  19. Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis
    Islam MA, Kundu S, Hassan R
    Curr Gene Ther, 2020;19(6):376-385.
    PMID: 32141417 DOI: 10.2174/1566523220666200306092556
    Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.
    Matched MeSH terms: Genetic Therapy*
  20. 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
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