Abstract:
:Recent advances in genome sequencing have greatly improved our ability to understand and identify the causes of genetic diseases. However, there remains an urgent need for innovative, safe, and effective treatments for these diseases. CRISPR-based genome editing systems have become important and powerful tools in the laboratory, and efforts are underway to translate these into patient therapies. Therapeutic base editing is one form of genome engineering that has gained much interest because of its simplicity, specificity, and effectiveness. Base editors are a fusion of a partially deactivated Cas9 enzyme with nickase function, together with a base-modifying enzyme. They are capable of precisely targeting and repairing a pathogenic mutation to restore the normal function of a gene, ideally without disturbing the rest of the genome. In the past year, research has identified new safety concerns of base editors and sparked new innovations to improve their safety. In this review, we provide an overview of the recent advances in the safety and effectiveness of therapeutic base editors and prime editing.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Carlaw TM,Zhang LH,Ross CJDdoi
10.1089/hum.2020.111subject
Has Abstractpub_date
2020-08-01 00:00:00pages
794-807issue
15-16eissn
1043-0342issn
1557-7422journal_volume
31pub_type
杂志文章abstract::Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.166
更新日期:2017-05-01 00:00:00
abstract::We studied hematopoietic progenitors from fetal baboon blood, marrow, and liver at four time points (125, 140, 160, and 175 days) during the third trimester (gestation approximately 180 days) to determine if fetal baboons might be an appropriate model for in utero gene therapy of hematopoietic stem cells (HSCs). Cells...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018742
更新日期:1999-03-01 00:00:00
abstract::Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.4-487
更新日期:1998-03-01 00:00:00
abstract::This Phase I study, "Ribozyme Gene Therapy of HIV-1 Infection" (UCSD HSC #971072, FDA BB-IND 6405), is a prospective, open-label trial of infusion of autologous gene-altered cells into asymptomatic HIV-1 seropositive individuals. The objectives of this trial are to test the safety, feasibility, and potential efficacy ...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.1998.9.16-2407
更新日期:1998-11-01 00:00:00
abstract::Gutted adenoviral (Ad) vectors have a greater cloning capacity and elicit less immune response than conventional Ad vectors. Unfortunately, clinical use of gutted vectors has been slowed by production difficulties, including low yield and a tendency for recombinant virus to emerge. These two problems are related, beca...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252809810
更新日期:2002-03-01 00:00:00
abstract::Human hematopoietic stem cells (HSCs) are poorly transduced by vectors based on adenovirus serotype 5 (Ad5). This is primarily due to the paucity of the coxsackievirus-Ad receptor on these cells. In an attempt to change the tropism of Ad5, we constructed a series of chimeric E1-deleted Ad5 vectors in which the shaft a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401753204562
更新日期:2001-11-01 00:00:00
abstract::Activation of T cells is necessary for efficient retroviral-mediated gene transfer. In addition, if the population of infused cells is to be limited to transduced cells, a means of positive selection is required. We describe a clinical scale procedure for activation of donor T cells with anti-CD3/CD28 beads followed b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252939087
更新日期:2002-05-20 00:00:00
abstract::La Crosse virus (LACV)-mediated encephalitis is the most frequently reported arboviral disease in the United States, but to date no vaccine against this virus is available. We have established a new animal model, genetically targeted mice lacking a functional interferon type I receptor (IFNAR-1). These mice show an ag...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017653
更新日期:1999-07-01 00:00:00
abstract::We previously demonstrated that intramuscular plasmid injection serves as a useful method of long-term systemic delivery of cytokines. In the present study, we assess intramuscular DNA injection as a means of systemically delivering interleukin 10 (IL-10), a cytokine with immunosuppressive properties, and preventing t...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.12-1701
更新日期:1998-08-10 00:00:00
abstract::Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. Unfortunately, viruses are limited in their ability to diffuse through tissue. This makes it virtually impossible to infect the majority of tumor cells in vivo and results in inadequate gene transfer. This p...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.8-1209
更新日期:1998-05-20 00:00:00
abstract::Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mut...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.9-1359
更新日期:1998-06-10 00:00:00
abstract::Diabetes mellitus is associated with increased risk of heart failure. It has been previously demonstrated in mice that a single injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in models of insulin resistance and improves the function of the failing heart. The present s...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.150
更新日期:2019-06-01 00:00:00
abstract::In summary, I will reiterate the five points I would like to leave with you today: First, the biological revolution has extraordinary power to do good. As long as the use of our new genetic knowledge is guided by the traditional ideals of the healing professions--to help improve the human condition without doing harm-...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1992.3.1-51
更新日期:1992-02-01 00:00:00
abstract::Administration of recombinant adenoviral (AdV) vectors to animals can lead to inflammatory and immune responses. For therapeutic indications in which repeated treatment is necessary, such as cystic fibrosis (CF), these responses can limit the therapeutic usefulness of the vector. In principle, the utility of the vecto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401300042348
更新日期:2001-03-20 00:00:00
abstract::Oncolytic measles virus (MV) encoding the human thyroidal sodium iodide symporter (MV-NIS) has proved to be safe after intraperitoneal or intravenous administration in patients with ovarian cancer or multiple myeloma, respectively, but it has not yet been administered through intratumoral injection in humans. Squamous...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.128
更新日期:2012-03-01 00:00:00
abstract::Adenovirus (Ad) vectors used for gene therapy are efficient in entering the infected cell and targeting their genome to the nucleus. To study the mechanism of the interaction between Ad and the nuclear envelope we have established an in vitro assay using rat liver nuclei incubated with serotype 5 Ad vector. Binding of...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017176
更新日期:1999-09-01 00:00:00
abstract::The T cell co-stimulatory molecule B7-1 was transduced into a poorly immunogenic murine neuroblastoma cell line (Neuro-2a, N-2a) alone or in combination with MHC class II genes to test the ability of these genes to stimulate antitumor immunity. N-2a cells transduced with B7-1 exhibited reduced tumorigenicity, whereas ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.17-2059
更新日期:1996-11-10 00:00:00
abstract::Mutations in the gene encoding the peroxisomal ATP-binding cassette transporter (ABCD1) cause elevations in very long-chain fatty acids (VLCFAs) and the neurodegenerative disease adrenoleukodystrophy (ALD). In most adults, this manifests as the spinal cord axonopathy adrenomyeloneuropathy (AMN). A challenge in virus-b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.079
更新日期:2019-05-01 00:00:00
abstract::Successful gene therapy approaches for metachromatic leukodystrophy (MLD), based either on hematopoietic stem/progenitor cells (HSPCs) or direct central nervous system (CNS) gene transfer, highlighted a requirement for high levels of arylsulfatase A (ARSA) expression to achieve correction of disease manifestations in ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.048
更新日期:2007-09-01 00:00:00
abstract::Bag-1 exerts powerful antiapoptotic effects by binding and stabilizing Bcl-2 and interacting with the tumor necrosis factor receptor type I-induced death signal. We examined the effects of overexpression of Bag-1 by ex vivo adenoviral gene transfer on cold (4 degrees C for 24 hr) ischemia/reperfusion (I/R) injury of r...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340260185120
更新日期:2002-08-10 00:00:00
abstract::Gene transfer of reporter genes may trigger immune responses against the heterologous protein resulting in shortening of gene expression and inflammation. We generated transgenic rats expressing the lacZ gene under the control of the human immunodeficiency virus type 1 (HIV-1) long-terminal repeat (LTR) (HIV-lacZ) to ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760128603
更新日期:2002-07-20 00:00:00
abstract::Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, α1-antitrypsin (AAT) disorder and hemophilia B. Ex...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.073
更新日期:2016-11-01 00:00:00
abstract::To achieve effective gene therapy, it is necessary to selectively and efficiently transfect therapeutic gene into targeted cells. In this study, we developed a combination method using mannosylated lipoplexes, which show selectivity to antigen-presenting cells such as macrophages and dendritic cells, and bubble liposo...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.106
更新日期:2010-01-01 00:00:00
abstract::Administration of plasmid/lipid complexes to the lung airways for the treatment of metastatic pulmonary diseases represents a new strategy of gene therapy. In this study we present evidence that intratracheal administration of a plasmid encoding murine IL-12 complexed with N-[1-(2,3-dioleyloxy)propyl)-N,N,N-trimethyla...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018481
更新日期:1999-03-20 00:00:00
abstract::Engineered measles virus (MV) strains deriving from the vaccine lineage represent a promising oncolytic platform and are currently being tested in phase I trials. In this study, we have demonstrated that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor act...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.158
更新日期:2012-04-01 00:00:00
abstract::Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector e...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.10-1487
更新日期:1998-07-01 00:00:00
abstract::Previously, we described a nonviral cytoplasmic gene therapy vector system based on the T7 autogene concept. This system has been shown to achieve rapid and high levels of gene expression in a variety of animal cells and tissues. To test the utility of the system in vivo tumor ablation, a T7 cancer gene therapy plasmi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.5-729
更新日期:1998-03-20 00:00:00
abstract::This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via wee...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2010.020
更新日期:2010-09-01 00:00:00
abstract::Silencing of Wnt antagonists with aberrant activation of Wnt signaling is a common phenomenon in various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. In this study, we tried to illuminate the impact of WIF-1 ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.005
更新日期:2007-04-01 00:00:00
abstract::Stem cell mobilization to injured tissue contributes to neovascularization, resulting in regeneration after myocardial infarction (MI). We previously showed that direct cardiac injection of a recombinant lentivirus (LV) that engineers expression of membrane-bound stem cell factor (mSCF) improves outcomes immediately a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.063
更新日期:2012-12-01 00:00:00