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2.
Nanoscale ; 13(30): 12848-12853, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477769

RESUMO

Nucleic acid nanostructures are promising biomaterials for the delivery of homologous gene therapy drugs. Herein, we report a facile strategy for the construction of target mRNA (scaffold) and antisense (staple strands) co-assembled RNA/DNA hybrid "origami" for efficient gene therapy. In our design, the mRNA was folded into a chemically well-defined nanostructure through RNA-DNA hybridization with high yield. After the incorporation of an active cell-targeting aptamer, the tailored RNA/DNA hybrid origami demonstrated efficient cellular uptake and controllable release of antisenses in response to intracellular RNase H digestion. The biocompatible RNA/DNA origami (RDO) elicited a noticeable inhibition of cell proliferation based on the silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This RDO-based nanoplatform provides a novel strategy for the further development of gene therapy.


Assuntos
Nanoestruturas , RNA , DNA/genética , Terapia Genética , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , RNA/genética
3.
Nanoscale ; 13(34): 14538-14551, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473182

RESUMO

The use of cell-penetrating peptides (CPPs), typically HIV-Tat, to deliver therapeutic genes for cancer treatment is hampered by the inefficient delivery and complicated uptake route of plasmid DNA (pDNA). On the one hand, surface charges, particle size and shape essentially contribute to the endocytosis pathway of Tat/pDNA nanocomplexes, and on the other hand, endogenous cellular factors dominantly determine their intracellular trafficking fate and biological outcome. Recent advances in surfactant-modified nanomaterial and dual molecular imaging technology have offered new opportunities for suicide gene therapy. In this study, we employed the cationic surfactant C16TAB to further condense Tat/pDNA nanocomplexes for improving their delivery efficiency and tested the therapeutic effect of Tat/pDNA/C16TAB (T-P-C) nanoparticles carrying the GCV-converted HSV-ttk suicide gene for ovarian cancer. The cellular endocytosis pathway and underlying signal mechanism of T-P-C nanoparticles were further determined. The obtained T-P-C nanoparticles exhibited a small size, positive surface charge, irregular granular shape and high pDNA encapsulation efficiency. The in vitro experiments showed that T-P-C nanoparticles mainly used the macropinocytosis pathway for uptake in ovarian cancer cells. Their internalization and payload gene expression were controlled by the Arf6 GTPase-dependent, Rab GTPase-activated signal axis. Further in vivo molecular imaging based on DF (Fluc-eGFP)-TF (RFP-Rluc-HSV-ttk) system showed that T-P-C nanoparticles significantly increased the targeted delivery and suicide gene therapy in a mouse model xenografted with human ovarian cancer. More importantly, Arf6-mediated macropinocytosis remarkably enhanced the delivery efficiency and suicide gene therapy effect of T-P-C nanoparticles. Therefore, these C16TAB-condensed Tat/pDNA nanoparticles combined with the dual molecular imaging strategy provides a novel intracellular delivery platform for high-efficient, precise suicide gene therapy of ovarian cancer.


Assuntos
Nanopartículas , Neoplasias Ovarianas , Animais , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Camundongos , Neoplasias Ovarianas/terapia , Plasmídeos , Transfecção
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474905

RESUMO

Bioreducible polyethylenimines (SSPEIs) are promising non-viral carriers for cancer gene therapy. However, the availability of significant gene transfection activity by SSPEIs remains a challenge. Herein, an essential step was taken to ascertain whether or not the disulfide bonds of SSPEIs play a critical role in promoting significant gene transfection activity in different tissues. Initially, a disulfide-linked linear polyethylenimine (denoted as SSLPEI) consisting of one 5.0 kDa LPEI main chain and three disulfide-linked 5.7 kDa LPEI grafts was designed and prepared to possess similar molecular weight with commercialized 25 kDa LPEI as a positive control. The SSLPEI could induce superior in vitro transfection activity in different cells to the LPEI control as well as low cytotoxicity. Notably, such enhanced in vitro transfection effect by the SSLPEI was more marked in type-II alveolar epithelial cells compared to different cancer cells. In a Balb/c nude mouse model bearing SKOV-3 tumor, the SSLPEI caused parallel level of transgene expression with the LPEI control in the tumor but significantly higher level in the mouse lung. Furthermore, the SSLPEI and LPEI groups afforded an identical antitumor efficacy against the SKOV-3 tumor via intravenous delivery of a shRNA for silencing VEGF expression in the tumor. However, via intravenous delivery of an interleukin-12 (IL-12) gene into metastatic lung cancers in a C57BL/6 mouse model, the SSLPEI group exerted markedly higher IL-12 expression level in the mouse lung and peripheral blood as compared to the LPEI group, thereby boosting IL-12 immunotherapy against the lung metastasis with longer medium survival time. The results of this work elicit that the disulfide bonds of SSPEIs play a pivotal role in enhancing gene transfection activity selectively in the lung tissue rather than solid tumor, enabling high translational potential of SSPEIs for non-viral gene therapy against metastatic lung cancers.


Assuntos
Neoplasias Pulmonares , Polietilenoimina , Animais , Dissulfetos , Terapia Genética , Interleucina-12/genética , Pulmão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Endogâmicos C57BL , Transfecção
5.
Blood Adv ; 5(17): 3333-3343, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477814

RESUMO

Orthologous proteins contain sequence disparity guided by natural selection. In certain cases, species-specific protein functionality predicts pharmacological enhancement, such as greater specific activity or stability. However, immunological barriers generally preclude use of nonhuman proteins as therapeutics, and difficulty exists in the identification of individual sequence determinants among the overall sequence disparity. Ancestral sequence reconstruction (ASR) represents a platform for the prediction and resurrection of ancient gene and protein sequences. Recently, we demonstrated that ASR can be used as a platform to facilitate the identification of therapeutic protein variants with enhanced properties. Specifically, we identified coagulation factor VIII (FVIII) variants with improved specific activity, biosynthesis, stability, and resistance to anti-human FVIII antibody-based inhibition. In the current study, we resurrected a panel of ancient mammalian coagulation factor IX (FIX) variants with the goal of identifying improved pharmaceutical candidates. One variant (An96) demonstrated 12-fold greater FIX activity production than human FIX. Addition of the R338L Padua substitution further increased An96 activity, suggesting independent but additive mechanisms. after adeno-associated virus 2 (AAV2)/8-FIX gene therapy, 10-fold greater plasma FIX activity was observed in hemophilia B mice administered AAV2/8-An96-Padua as compared with AAV2/8-human FIX-Padua. Furthermore, phenotypic correction conferred by the ancestral variant was confirmed using a saphenous vein bleeding challenge and thromboelastography. Collectively, these findings validate the ASR drug discovery platform as well as identify an ancient FIX candidate for pharmaceutical development.


Assuntos
Fator IX , Hemofilia B , Animais , Testes de Coagulação Sanguínea , Fator IX/genética , Terapia Genética , Hemofilia B/genética , Hemofilia B/terapia , Hemorragia , Camundongos
6.
Gene ; 803: 145889, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34371094

RESUMO

Although seen as a revolution in modern science, gene therapy has been plagued by failed clinical trials and controversial ethics in the last thirty years. Moreover, there is no comprehensive, in-depth, high-quality analysis of global gene therapy patents. This paper proposes a method to correctly retrieve patents to address the issue and use it for the patent landscape. The results show the global patent landscape of gene therapy, with the United States dominating the field, while China has emerged as a leader in recent years. For various reasons, the EU, Korea, and Japan lag in the development of patented technologies. China has edged closer to the US in both live and indefinite patents, with the Chinese Academy of Military Medical Sciences and the Chinese Academy of Sciences leading the way, surpassing primary applicants such as the US Department of Health and Human Services, the University of California, and the University of Pennsylvania. The study also reveals four broad categories of technologies that have been extensively studied in gene therapy: basic biology of the gene and diseases, diseases being treated, gene delivery methods, and potential adverse events. What is more, Adeno-Associated Virus, Retrovirus, and Lentivirus are the most prevalent gene therapy delivery vectors after 2014. The industrial development trend revealed in this paper can provide an evidence-based basis for scientific research management and decision-making.


Assuntos
Terapia Genética , Vetores Genéticos/classificação , Patentes como Assunto , China , Dependovirus/genética , União Europeia , Humanos , Japão , Lentivirus/genética , República da Coreia , Retroviridae/genética , Estados Unidos
7.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445083

RESUMO

Intronic splicing silencer N1 (ISS-N1) located within Survival Motor Neuron 2 (SMN2) intron 7 is the target of a therapeutic antisense oligonucleotide (ASO), nusinersen (Spinraza), which is currently being used for the treatment of spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. The discovery of ISS-N1 as a promising therapeutic target was enabled in part by Anti-N1, a 20-mer ASO that restored SMN2 exon 7 inclusion by annealing to ISS-N1. Here, we analyzed the transcriptome of SMA patient cells treated with 100 nM of Anti-N1 for 30 h. Such concentrations are routinely used to demonstrate the efficacy of an ASO. While 100 nM of Anti-N1 substantially stimulated SMN2 exon 7 inclusion, it also caused massive perturbations in the transcriptome and triggered widespread aberrant splicing, affecting expression of essential genes associated with multiple cellular processes such as transcription, splicing, translation, cell signaling, cell cycle, macromolecular trafficking, cytoskeletal dynamics, and innate immunity. We validated our findings with quantitative and semiquantitative PCR of 39 candidate genes associated with diverse pathways. We also showed a substantial reduction in off-target effects with shorter ISS-N1-targeting ASOs. Our findings are significant for implementing better ASO design and dosing regimens of ASO-based drugs.


Assuntos
Atrofia Muscular Espinal/terapia , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos/farmacologia , Transcriptoma , Células Cultivadas , Terapia Genética , Humanos , Íntrons/efeitos dos fármacos , Atrofia Muscular Espinal/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Transcriptoma/efeitos dos fármacos
8.
Nat Commun ; 12(1): 5180, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462437

RESUMO

Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. Restoring the Ca2+ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp-/-), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Cardiomiopatias/genética , Cardiomiopatias/terapia , Terapia Genética , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Oligonucleotídeos Antissenso/genética , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatias/metabolismo , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Oligonucleotídeos Antissenso/metabolismo , Ratos , Ratos Endogâmicos Lew
9.
Indian J Ophthalmol ; 69(9): 2257-2265, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34427196

RESUMO

Over 2 million people worldwide are suffering from gene-related retinal diseases, inherited or acquired, and over 270 genes have been identified which are found to be responsible for these conditions. This review article touches upon the mechanisms of gene therapy, various enzymes of the visual cycle responsible for different genetic diseases, Luxturna-the first US Food and Drug Administration (FDA)-approved therapeutic gene product, and several ongoing trials of gene therapy for age-related macular degeneration. Gene therapy has tremendous potential for retinal conditions due to its ease of accessibility, immune-privileged status, and tight blood-retinal barriers, limiting systemic side effects of the drug. In recent years, advances in gene therapy in retinal conditions have increasing significantly, with progress in cell-specific targeting and transduction efficiency of gene products through the use of adeno-associated viral vectors (AAVs), suggesting that even greater success in future clinical trials is possible.


Assuntos
Degeneração Macular , Preparações Farmacêuticas , Doenças Retinianas , Terapia Genética , Vetores Genéticos , Humanos , Degeneração Macular/terapia , Doenças Retinianas/genética , Doenças Retinianas/terapia , Estados Unidos
10.
Vestn Oftalmol ; 137(4): 145-151, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34410070

RESUMO

The article presents recent worldwide achievements in the area of diagnosis and treatment of inherited retinal degenerations (IRDs) from the standpoint of ophthalmic genetics. Clinical studies conducted in patients with Leber congenital amaurosis and retinitis pigmentosa caused by biallelic mutations in the RPE65 gene have provided the basis for future genes studies associated with IRDs. The conducted studies highlight the importance of fundamental understanding of function of the gene, timely diagnosis and study of natural history of the disease. Currently, surgical techniques are being improved for the efficient delivery of gene preparations to target cells, as well as the criteria for evaluating treatment outcomes.


Assuntos
Amaurose Congênita de Leber , Degeneração Retiniana , Retinite Pigmentosa , Terapia Genética , Humanos , Amaurose Congênita de Leber/diagnóstico , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/terapia , Mutação , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/genética , Degeneração Retiniana/terapia , Retinite Pigmentosa/diagnóstico , Retinite Pigmentosa/genética , Retinite Pigmentosa/terapia
11.
FASEB J ; 35(9): e21766, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34383976

RESUMO

Bardet-Biedl syndrome (BBS) is a hereditary genetic disorder that results in numerous clinical manifestations including olfactory dysfunction. Of at least 21 BBS-related genes that can carry multiple mutations, a pathogenic mutation, BBS1M390R, is the single most common mutation of clinically diagnosed BBS outcomes. While the deletion of BBS-related genes in mice can cause variable penetrance in different organ systems, the impact of the Bbs1M390R mutation in the olfactory system remains unclear. Using a clinically relevant knock-in mouse model homozygous for Bbs1M390R, we investigated the impact of the mutation on the olfactory system and tested the potential of viral-mediated, wildtype gene replacement therapy to rescue smell loss. The cilia of olfactory sensory neurons (OSNs) in Bbs1M390R/M390R mice were significantly shorter and fewer than those of wild-type mice. Also, both peripheral cellular odor detection and synaptic-dependent activity in the olfactory bulb were significantly decreased in the mutant mice. Furthermore, to gain insight into the degree to which perceptual features are impaired in the mutant mice, we used whole-body plethysmography to quantitatively measure odor-evoked sniffing. The Bbs1M390R/M390R mice showed significantly higher odor detection thresholds (reduced odor sensitivity) compared to wild-type mice; however, their odor discrimination acuity was still well maintained. Importantly, adenoviral expression of Bbs1 in OSNs restored cilia length and re-established both peripheral odorant detection and odor perception. Together, our findings further expand our understanding for the development of gene therapeutic treatment for congenital ciliopathies in the olfactory system.


Assuntos
Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/terapia , Ciliopatias/genética , Ciliopatias/terapia , Percepção Olfatória/genética , Animais , Cílios/genética , Modelos Animais de Doenças , Feminino , Terapia Genética/métodos , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Mutação/genética , Bulbo Olfatório/patologia , Células Receptoras Sensoriais/patologia , Olfato/genética
12.
Elife ; 102021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34382938

RESUMO

A tool that analyzes the genome of parasites found in the blood of malaria patients can help inform policy decisions on how best to tackle the rise in drug-resistant infections.


Assuntos
Antimaláricos , Malária , Antimaláricos/uso terapêutico , Engenharia Genética , Terapia Genética , Humanos , Malária/tratamento farmacológico , Plasmodium falciparum/genética
13.
Nat Commun ; 12(1): 4934, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400638

RESUMO

Rhodopsin (RHO) gene mutations are a common cause of autosomal dominant retinitis pigmentosa (ADRP). The need to suppress toxic protein expression together with mutational heterogeneity pose challenges for treatment development. Mirtrons are atypical RNA interference effectors that are spliced from transcripts as short introns. Here, we develop a novel mirtron-based knockdown/replacement gene therapy for the mutation-independent treatment of RHO-related ADRP, and demonstrate efficacy in a relevant mammalian model. Splicing and potency of rhodopsin-targeting candidate mirtrons are initially determined, and a mirtron-resistant codon-modified version of the rhodopsin coding sequence is validated in vitro. These elements are then combined within a single adeno-associated virus (AAV) and delivered subretinally in a RhoP23H knock-in mouse model of ADRP. This results in significant mouse-to-human rhodopsin RNA replacement and is associated with a slowing of retinal degeneration. This provides proof of principle that synthetic mirtrons delivered by AAV are capable of reducing disease severity in vivo.


Assuntos
Terapia Genética , RNA/genética , Retinite Pigmentosa/genética , Retinite Pigmentosa/terapia , Animais , Dependovirus/genética , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Vetores Genéticos , Células HEK293 , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA/metabolismo , Interferência de RNA , Splicing de RNA , Retina , Degeneração Retiniana , Rodopsina/genética , Rodopsina/metabolismo
14.
J Theor Biol ; 528: 110850, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34339731

RESUMO

Both anti-angiogenesis and gene therapy involve complex processes depending on non-point parameters belonging to a space of values. To successfully overcome the challenges involved in their therapeutic approaches, there is a need to analyze the sensitivity of these parameters. In this paper, a new mathematical model that combines immune system stimulations, inflammatory processes associated with tumor development, and gene therapy aimed at enhancing the efficacy of both treatments are explored. Using the global sensitivity methods of Sobol and Morris, the most important parameters are estimated. Estimation of the sensitivity variance revealed a strong interdependence between the parameters. Also, determinations of the conditions for effective therapy lead to a target of reducing the cancer cell numbers by at least 50%. This opened the way for delimiting the parameter spaces making it possible to reach the treatment target in addition to enhancing the estimation of the minimum time of remission. The combination of therapies and sensitivity analysis have demonstrated the robustness of therapy success.


Assuntos
Neoplasias , Terapia Viral Oncolítica , Terapia Genética , Humanos , Imunoterapia , Modelos Teóricos , Neoplasias/genética , Neoplasias/terapia
16.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360621

RESUMO

Metabolic syndrome (MetS) is a set of complex, chronic inflammatory conditions that are characterized by central obesity and associated with an increased risk of cardiovascular diseases. In recent years, microRNAs (miRNAs) have become an important type of endocrine factors, which play crucial roles in maintaining energy balance and metabolic homeostasis. However, its unfavorable properties such as easy degradation in blood and off-target effect are still a barrier for clinical application. Nanosystem based delivery possess strong protection, high bioavailability and control release rate, which is beneficial for success of gene therapy. This review first describes the current progress and advances on miRNAs associated with MetS, then provides a summary of the therapeutic potential and targets of miRNAs in metabolic organs. Next, it discusses recent advances in the functionalized development of classic delivery systems (exosomes, liposomes and polymers), including their structures, properties, functions and applications. Furthermore, this work briefly discusses the intelligent strategies used in emerging novel delivery systems (selenium nanoparticles, DNA origami, microneedles and magnetosomes). Finally, challenges and future directions in this field are discussed provide a comprehensive overview of the future development of targeted miRNAs delivery for MetS treatment. With these contributions, it is expected to address and accelerate the development of effective NA delivery systems for the treatment of MetS.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Síndrome Metabólica/terapia , MicroRNAs/uso terapêutico , Nanoestruturas , Sistemas de Liberação de Medicamentos/tendências , Exossomos , Humanos , Lipossomos
17.
Viruses ; 13(7)2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34372550

RESUMO

Persistent hepatitis B virus (HBV) infection remains a serious medical problem worldwide, with an estimated global burden of 257 million carriers. Prophylactic and therapeutic interventions, in the form of a vaccine, immunomodulators, and nucleotide and nucleoside analogs, are available. Vaccination, however, offers no therapeutic benefit to chronic sufferers and has had a limited impact on infection rates. Although immunomodulators and nucleotide and nucleoside analogs have been licensed for treatment of chronic HBV, cure rates remain low. Transcription activator-like effector nucleases (TALENs) designed to bind and cleave viral DNA offer a novel therapeutic approach. Importantly, TALENs can target covalently closed circular DNA (cccDNA) directly with the potential of permanently disabling this important viral replicative intermediate. Potential off-target cleavage by engineered nucleases leading to toxicity presents a limitation of this technology. To address this, in the context of HBV gene therapy, existing TALENs targeting the viral core and surface open reading frames were modified with second- and third-generation FokI nuclease domains. As obligate heterodimers these TALENs prevent target cleavage as a result of FokI homodimerization. Second-generation obligate heterodimeric TALENs were as effective at silencing viral gene expression as first-generation counterparts and demonstrated an improved specificity in a mouse model of HBV replication.


Assuntos
Vírus da Hepatite B/genética , Hepatite B/tratamento farmacológico , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética , Animais , Animais não Endogâmicos , Antivirais/uso terapêutico , Linhagem Celular , Vírus de DNA/genética , DNA Circular , DNA Viral/genética , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Modelos Animais de Doenças , Endonucleases/genética , Feminino , Terapia Genética/métodos , Células HEK293 , Células Hep G2 , Hepatite B/genética , Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Humanos , Camundongos , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/uso terapêutico , Replicação Viral/genética
18.
Nat Med ; 27(8): 1311, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34385703
19.
Gene ; 805: 145906, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34411650

RESUMO

Cancer is becoming one of the deadliest disease in both developed as well as developing countries and continuous effort is being made to find innovative therapies for myriad types of cancers that afflict the human body. Therapeutic options for cancer have grown exponentially over the time but we are quite a way off from finding a magic bullet that can help cure cancer and based on the current evidence we may never find a catch all cure ever and it becomes crucial that we keep on innovating and find multiple ways to attack the menace of this dreaded disease. Many patients suffer recurrence of disease and require second-line or in some cases more than two lines of treatment. In this review article we have discussed the available therapies along with the newer advancements that have been made in cancer therapy. Latest developments in treatment of various cancers that have been discussed include gene editing using CRISPR/Cas9, theranostics, viral mediated therapy, artificial intelligence, tumor infiltrating lymphocyte therapy, etc.


Assuntos
Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão/tendências , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Edição de Genes/tendências , Terapia Genética/métodos , Humanos , Medicina de Precisão/métodos
20.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445243

RESUMO

Nanomaterials are currently being developed for the specific cell/tissue/organ delivery of genetic material. Nanomaterials are considered as non-viral vectors for gene therapy use. However, there are several requirements for developing a device small enough to become an efficient gene-delivery tool. Considering that the non-viral vectors tested so far show very low efficiency of gene delivery, there is a need to develop nanotechnology-based strategies to overcome current barriers in gene delivery. Selected nanostructures can incorporate several genetic materials, such as plasmid DNA, mRNA, and siRNA. In the field of nanotechnologies, there are still some limitations yet to be resolved for their use as gene delivery systems, such as potential toxicity and low transfection efficiency. Undeniably, novel properties at the nanoscale are essential to overcome these limitations. In this paper, we will explore the latest advances in nanotechnology in the gene delivery field.


Assuntos
Terapia Genética , Nanoestruturas/uso terapêutico , Nanotecnologia , Transfecção , Animais , Humanos
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