遗传学实验技术

In the new era of population genomics, surveys of genetic polymorphism (“genome scans”) offer the opportunity to distinguish locus-specific from genome-wide effects at many loci. Identifying presumably neutral regions of the genome that are assumed to be influenced by genome-wide eff ...

When searching for loci possibly under selection in the genome, an alternative to population genetics theoretical models is to establish allele distribution models (ADM) for each locus to directly correlate allelic frequencies and environmental variables such as precipitatio ...

Methods for estimating quantitative trait heritability in wild populations have been developed in recent years which take advantage of the increased availability of genetic markers to reconstruct pedigrees or estimate relatedness between individuals, but their applicati ...

Fetal gene transfer has been studied in various animal models, including rabbits, guinea pigs, cats, dogs, and nonhuman primate; however, the most common model is the rodent, particularly the mouse. There are numerous advantages to mouse models, including a short gestation time of around 20 day ...

Large animal experiments are vital in the field of prenatal gene therapy, to allow translation from small animals into man. Sheep provide many advantages for such experiments. They have been widely used in research into fetal physiology and pregnancy and the sheep fetus is a similar size to that in t ...

Intrauterine gene therapy (IUGT) potentially enables the treatment and possible cure of monogenic �diseases that cause severe fetal damage. The main benefits of this approach will be the ability to correct the disorder before the onset of irreversible pathology and inducing central im ...

Safety is an absolute prerequisite for introducing any new therapy, and the need to monitor the consequences of administration of both vector and transgene to the fetus is particularly important. The unique features of fetal development that make it an attractive target for gene therapy, su ...

Surrogate genetically encoded markers have been utilized in order to analyze gene transfer efficacy, location, and persistence. These marker genes have greatly accelerated the development of gene transfer vectors for the ultimate application of gene therapy using therapeutic g ...

So far no systematic studies have been conducted to investigate developmental aberrations after prenatal gene transfer in mice. Here, we suggest procedures for such observations to be applied, tested and improved in further in utero gene therapy experiments. They are based on our own exper ...

Gene delivery by integrating vectors has the potential to cause genotoxicity in the host by insertional mutagenesis (IM). Previously, the risk of IM by replication incompetent retroviral vectors was believed to be small. However, the recent observation of leukaemic events due to gamma re ...

The still experimental nature of prenatal gene therapy carries a certain degree of risk, both for the pregnant mother as well as for the fetus. Some of the risks are procedural hazards already known from more conventional fetal medicine interventions. Others are more specific to gene therapy su ...

Prenatal gene therapy aims to deliver genes to cells and tissues early in prenatal life, allowing correction of a genetic defect, before irreparable tissue damage has occurred. In contrast to postnatal gene therapy, prenatal application may target genes to a large population of stem cells, a ...

This introductory chapter provides a short review of the ideas and practical approaches that have led to the present and perceived future development of prenatal gene therapy. It summarizes the advantages and the potential adverse effects of this novel preventive and therapeutic appr ...

This chapter gives a comparative review of the different vector systems applied to date in prenatal gene therapy experiments highlighting the need for versatility and choice for application in accordance with the actual aim of the study. It reviews the key characteristics of the four main ge ...

Vectors based on adeno-associated virus (AAV) show great promise for safe, efficacious therapeutic gene transfer in extensive pre-clinical data and, recently, in clinical trials. Careful vector design and choice from a range of natural or synthetic pseudotypes allow targeted, effic ...

Adenoviruses have many attributes, which have made them one of the most widely investigated vectors for gene therapy applications. These include ease of genetic manipulation to produce replication-deficient vectors, ability to readily generate high titer stocks, efficiency of g ...

Vectors derived from the Retroviridae family have several attributes required for successful gene delivery. Retroviral vectors have an adequate payload size for the coding regions of most genes; they are safe to handle and simple to produce. These vectors can be manipulated to target diff ...

Gene therapy vectors based on viruses are the most effective gene delivery systems in use today and although efficient at gene transfer their potential toxicity (Hacein-Bey-Abina et al., Science 302:415–419, 2003) provides impetus for the development of safer non-viral alternatives. An ...

Prenatal stem cell therapy has broad potential for therapeutic application. “Stem cells” of interest include multipotent adult-derived stem cells, cord blood, amniotic fluid, or fetal stem cells, and embryonic or induced pluripotent stem cells. Potential manipulations of stem cel ...

Testing in animal models is an essential requirement during development of prenatal gene therapy for �clinical application. Some information can be derived from cell lines or cultured fetal cells, such as the efficiency of gene transfer and the vector dose that might be required. Fetal tiss ...