L’un des principaux défis de la thérapie génique est d’identifier un vecteur sûr capable d’assurer un transfert efficace et une expression soutenue d’un gène d’intérêt thérapeutique dans les cellules cibles. L’émergence de vecteurs plasmidiques de nouvelles générations a permis d’atteindre ces objectifs et de considérer la thérapie génique non virale comme une alternative prometteuse aux vecteurs viraux pour le traitement de maladies génétiques ou acquises. Appartenant à ces nouvelles générations, les dérivés du vecteur pFAR4 sont des miniplasmides dépourvus de gène de résistance à un antibiotique. Leur propagation dans les cellules d’Escherichia coli est basée sur la suppression d’une mutation non-sens de type ambre introduite dans un gène essentiel de la souche productrice, permettant ainsi d’éliminer les risques associés à l’utilisation de gène de résistance à un antibiotique tout en diminuant la taille du vecteur. Le but de cette thèse est d’étudier le potentiel de ces vecteurs dans deux contextes de thérapie génique non virale : Dans une première approche, le potentiel du vecteur pFAR4 a été évalué pour l’expression d’un gène thérapeutique dans le foie de souris. Pour ce faire, un dérivé de ce vecteur exprimant le gène Sgsh à partir d’un promoteur spécifique des hépatocytes et codant la protéine sulfamidase, protéine défectueuse chez les patients souffrant de la maladie de Sanfilippo de type A, a été administré par injection hydrodynamique à des souris. Nous avons montré que le vecteur pFAR4 promeut dans le foie une expression élevée et soutenue de la sulfamidase, qui décline rapidement lorsque le gène Sgsh est administré par un vecteur contenant un gène de résistance à la kanamycine. Dans le cadre de cette étude, il a été établi que le profil d’expression obtenu avec le vecteur pFAR4 n’est pas lié à son insertion dans le génome des hépatocytes mais résulte, de par sa taille réduite, d’une protection contre les phénomènes d’extinction de transgène couramment observés in vivo avec les vecteurs conventionnels. Dans une seconde approche, le vecteur pFAR4 a été combiné à la technologie Sleeping Beauty (SB), dont l’un des constituants majeurs est la transposase hyperactive SB100X qui promeut la transposition d’un transgène, en l’excisant du plasmide qui le porte et en l’insérant dans le génome des cellules hôtes. Cette combinaison a été étudiée in vitro dans des cellules HeLa, en utilisant un transposon contenant soit le gène de résistance à la néomycine soit le gène codant la protéine fluorescente Vénus. Nous avons ainsi montré que le plasmide pFAR4 constituait un vecteur efficace pour les composants du système SB et que la combinaison pFAR4/SB conduisait à un taux de transgénèse augmenté par rapport à une association avec des plasmides conventionnels. Cette efficacité élevée résulte d’un niveau de transfection et d’un taux d’excision augmentés, tous deux favorisés par la taille réduite du plasmide. La combinaison pFAR4/SB devrait prochainement être utilisée pour transférer le gène codant le facteur anti-angiogénique PEDF (Pigment Epithelium-Derived Factor) à des cellules primaires de l’épithélium pigmentaire de la rétine ou de l’iris dans deux essais cliniques (Phase I/II) de thérapie génique ex vivo pour le traitement de la dégénérescence maculaire liée à l’âge (DMLA). / One of the main challenges in gene therapy is to identify safe vectors that promote an efficient gene delivery and a sustained therapeutic transgene expression level in targeted cells. The development of novel plasmid vectors allowed to reach these objectives and to consider non-viral gene therapy approaches as attractive alternatives to treat genetic and acquired disorders. The pFAR4 vector is a novel antibiotic-free mini-plasmid. In Escherichia coli, its propagation is based on the suppression of an amber nonsense mutation introduced into an essential gene, thus eliminating safety concerns classically attributed to antibiotic resistance markers present on conventional plasmid DNA vectors and allowing a reduction in plasmid size. The aim of this work was to investigate the potential of pFAR4 as a gene vector in two different non-viral gene therapy approaches. In a first approach, the potential of the pFAR4 vector was assessed for the expression of a therapeutic gene in mouse liver. To this end, a pFAR4 derivative expressing the Sgsh gene from a liver-specific promoter and coding the sulfamidase, an enzyme deficient in patients suffering from the Sanfilippo A disease, was tail vein hydrodynamically injected into mouse liver. We showed that the pFAR4 derivative promoted a high and prolonged sulfamidase expression which rapidly declined when the same expression cassette was delivered by a conventional plasmid containing a kanamycin resistance marker. It was established that the superior expression profile obtained with the pFAR4 derivative did not result from its integration in host genome but seemed to benefit from protection against transcriptional silencing. In a second approach, the pFAR4 vector was combined to the Sleeping Beauty transposon system that mediates transgene integration into host genomes, after its excision from a plasmid donor by the hyperactive SB100X transposase, in order to obtain a long-term expression in dividing cells. This combination was studied in vitro, delivering either the neomycin resistance gene or the fluorescent Venus protein-encoding gene into HeLa cells. We showed that the combination pFAR4/SB led to an increased transgenesis rate in comparison to the association of SB with conventional plasmids. The pFAR4/SB combination seemed to benefit from an elevated transfection efficiency and a higher excision rate, resulting from the reduced size of the pFAR4 vector. The two technologies should be soon used for the delivery of the anti-angiogenic pigment epithelium-derived factor (PEDF) gene into autologous primary pigment epithelial cells, in the context of two PhaseI/II clinical trials based on an ex vivo gene therapeutic approach for the treatment of neovascular age-related macular degeneration (nAMD).

Transposons sind genetische Elemente, die fähig sind, sich innerhalb des Genoms zu bewegen. Sleeping Beauty (SB) gehört zur Tc1/mariner-Superfamilie von Transposons. SB wurde aus molekularen Fossilien rekonstruiert um u.a. einen sicheren und effizienten Vektor für die Gentherapie zu schaffen. Zu diesem Zweck ist es notwendig, den Mechanismus der SB-Transposition und deren Regulation, die Aktivitäten des Proteins und den Einfluss von Wirtsfaktoren genau zu verstehen. In meiner Arbeit habe ich die einzelnen Schritte des Transpositionsprozesses und die Bildung des sogenannten paired-end complex (PEC) – eine Voraussetzung für die folgenden katalytischen Reaktionen – untersucht. Zusätzlich habe ich versucht, einen in vitro Transpositionstest für SB zu etablieren. SB gehört zur IR/DR-Gruppe der Tc1/mariner-Superfamilie. Im Gegensatz zu mariner-like-Elementen ist die IR/DR-Struktur von SB durch lange IRs mit insgesamt vier Bindestellen für die Transposase gekennzeichnet. Ich habe die Fähigkeit dieser beiden Transposon-Systeme zum Ausschneiden eines Transposonendes ohne die Beteiligung des anderen Endes im PEC getestet. Solche unpräzise Transposition kann zu genomic rearrangements führen. Meine Ergebnisse zeigen, dass SB zwar imstande ist, ein einzelnes Transposonende auszuschneiden, dies geschieht jedoch weit weniger effizient als bei mariner-like-Elementen. Die Unterdrückung unpräziser Transpositionsereignisse ist ein Ergebnis der besseren durch die IR/DR-Struktur bedingten Regulation von SBs Transposition. Die Komplexität der IRs in Kombination mit der zweiteiligen DNA-Bindedomäne von SB kann als Mittel einer raffinierten Regulation des Transpositionsprozesses angesehen werden, welche das Genom vor anormalen Transpositionsereignissen schützt. Die Ergebnisse meiner Arbeit legen ein Modell nahe, in dem die Bildung des PEC während der Transposition von SB ein höchst genau regulierter Prozess ist, der durch die DNA-Protein- und Protein-Protein-Bindeaffinitäten geleitet wird. / Transposons are pieces of DNA able to move within the genomes. Sleeping Beauty is a verterbrate Tc1/mariner transposon reconstructed from molecular fossils to create a safe and efficient vector for gene therapy. For that purpose it is important to deeply understand the mechanism and regulation of the SB transposition, the activities of the transposase and influence of host factors on the process. Therefore, in this project I studied the single steps of the transposition reaction and formation of the paired-end complex (PEC) which is a prerequisite for the subsequent catalytic steps. Additionally, I tried to establish an in vitro transposition assay for Sleeping Beauty that would serve an easy assay for testing the system and probe mechanisms affecting the regulation of transposition activity. Sleeping Beauty belongs to the IR/DR subfamily of the Tc1/mariner-like transposons. In contrast to mariner-like elements the IR/DR structure of SB is characterized by long IRs with four binding sites for the transposase. I compared the ability of the two systems to perform cleavage of the single transposon end without including the second end in the PEC. Such imprecise transposition can lead to genome rearrangements. My results show that SB is capable of single-end cleavage; however, to much lower extent than the mariner-like element. Lower number of imprecise transposition events is a result of better regulation of the SB transposition imposed by the IR/DR stucture. The complexity of the inverted repeats together with the bipartite DNA-binding domain of SB might offer means for more sophisticated regulation of the transposition process, thereby protecting the genome from aberrant transposition events. I propose that complex formation in SB transposition is a strictly regulated ordered assembly process, guided by DNA-protein and protein-protein interaction interfaces of the DNA-binding subdomains. Obtained results allowed me to draw a model how the paired-end complex is formed.

Sleeping Beauty (SB) Transposon-basierte Vektoren werden als Alternative zu viralen Vektoren für T-Zell-Gentherapie erforscht und ermöglichen eine schnelle und kostengünstige Genmanipulation von T-Zellen. Die Verwendung von Transposon-Vektoren erfordert jedoch die DNA-Elektroporation von T-Zellen, die sich schädlich auf T-Zellen auswirkt. DNA-elektroporierte T-Zellen weisen eine verringerte Lebensfähigkeit und eine verzögerte Aktivierung nach Stimulation des T-Zell-Rezeptors (TCR) auf. Um die Nachteile der Transposon-basierten T-Zell-Genmanipulation zu überwinden, haben wir neuartige SB-Vektoren entwickelt. Durch die Kombination von SB Transposon-basierten Minicircle-Vektoren mit SB100X Transposase-mRNA konnten T-Zellen effizient genmodifiziert werden. Unser Ansatz reduzierte die T-Zell-Mortalität und steigerte gleichzeitig die Transfektionseffizienz. Mit diesen neuartigen Vektoren wurde die stabile Expression verschiedener TCRs und CARs in über 50% der eingesetzten T-Zellen erreicht. Gentechnisch manipulierte T-Zellen konnten Antigen-spezifisch stimuliert werden und zeigten effiziente Zytokin-Sekretion und Tumorzell-Lyse. Weiterhin haben wir miRNAs entwickelt, die die Expression der endogenen TCR-Ketten unterdrücken. Der Einbau dieser miRNAs in die TCR-Expressionskassette erhöhte die Oberflächenexpression des therapeutischen TCRs, verringerte die Fehlpaarung mit endogenen TCR-Ketten und erhöhte die T-Zell-Funktionalität. Ein direkter Vergleich von SB- und Virus-modifizierten T-Zellen zeigte sowohl in vitro als auch in vivo eine vergleichbare Wirksamkeit der modifizierten T-Zellen hinsichtlich Zytokin-Sekretion, Tumorzell-Lyse und Tumorkontrolle. In dieser Arbeit konnte gezeigt werden, dass SB Minicircle-Vektoren die Herstellung von genetisch modifizierten T-Zellen ermöglichen und diese Tumor-spezifische Wirksamkeit aufweisen. Dieser Ansatz könnte die Herstellung therapeutischer T-Zellen für die personalisierte T-Zell-Gentherapie vereinfachen und beschleunigen. / Sleeping Beauty (SB) transposon-based vectors have entered clinical trials as an alternative to viral vectors for T cell gene therapy, offering time- and cost-efficient engineering of therapeutic T cells. However, transposon vectors require DNA electroporation into T cells, which we found to cause adverse effects. T cell viability was decreased, and DNA-transfected T cells showed delayed activation upon T cell receptor (TCR) stimulation regarding blast formation and proliferation. To overcome the limitations of transposon-based T cell engineering, we investigated the effect of DNA electroporation on T cells and developed novel SB vectors. T cells could efficiently be engineered with Sleeping Beauty vectors by combining SB transposon minicircles and SB100X transposase mRNA. Our approach reduced T cell mortality and substantially enhanced transfection efficiency. We achieved stable expression of several TCRs and CARs in more than 50% of the transfected T cells compared to 15% when conventional plasmids were used. T cells engineered to express a tumor-specific TCR mediated effective tumor cell lysis and cytokine secretion upon antigen-specific stimulation. Furthermore, we developed miRNAs to silence the expression of the endogenous TCR chains. Incorporation of these miRNAs into the TCR expression cassette increased surface expression of the therapeutic TCR, diminished mispairing with endogenous TCR chains, and enhanced T cell functionality. Importantly, a direct comparison of SB minicircle- and RV-engineered T cells in vitro as well as in vivo demonstrated equal T cell efficacy with regards to cytokine release, tumor cell lysis and tumor control. We demonstrated that SB minicircles enable the generation of gene-modified T cells with tumor-specific reactivity. Our approach facilitates the manufacturing of therapeutic T cells with superior biosafety and accelerates the generation of patient-specific T cell products for personalized T cell gene therapy.

As the costs for mounting opera, ballet and orchestral concerts rise and as their audiences dwindle, piano transcriptions of works orchestrated for such concerts can be a viable way of disseminating the music more widely than if the music was presented only in its original form. With this in mind, it can be argued that piano transcriptions of music originally written for instrumental ensemble is still a viable form of musical expression, because the piano is still the most widely used medium for the performance of art music in the Western world. Transcriptions of instrumental and vocal music expand the listening audience for a composer's music while they also increase the repertoire of music for the piano for both amateurs and professionals. The CD recording has the aim of providing a reference on which to base an appreciation of Pletnev's work. As the orchestral score is quite well known, the differentiation created by Pletnev, and the quality of his work, can be immediately perceived by hearing the execution of his scores and being able to cross reference his reductions with the original score. Timing references for the piano score have been included to further facilitate this cross-referencing. This thesis comprises two parts: 1. A performance CD of Stravinsky's Petrouchka (1922 piano four-hand version) and Tchaikovsky's Sleeping Beauty (1999 solo piano transcription by Mikhail Pletnev). This accounts for 75% of the thesis. 2. An exegesis, analysing selected portions of the orchestral score of Tchaikovsky's The Sleeping Beauty Op.66 and Pletnev's piano transcription suite, prefaced by an overview of piano transcriptions from Liszt to Pletnev. This accounts for 25% of the thesis. The exegesis argues that, while seeking to recreate the colour and drama of Tchaikovsky's orchestral score within the context of a virtuosic piano solo, Pletnev has managed to transcribe Tchaikovsky's score faithfully with minimal alterations.

When attempting to convey certain political or ideological agendas in literary texts maintaining specific writing strategies can work as a useful tool. From a feminist perspective the use of écriture feminine as a means of undermining patriarchy has been largely neglected as well as misunderstood by many feminists. However, as argued in this essay, écriture feminine is not only a useful tool for pursuing a feminist agenda, but is also something that needs to be discussed due to the many misunderstandings of it. Resting on the theoretical perspectives of Judith Butler, Hélène Cixous, Antonio Gramsci, Eve Kosofsky Sedgwick and Richard Slotkin this essay investigates Angela Carter’s short story “The Lady of the House of Love” in relation to écriture feminine by exploring how the text rejects patriarchy and its idea of the gender binary. In this short story Carter re-works the classic Sleeping Beauty fairy tale and provides us with a feminist’s version of it. The main thesis of this essay is therefore that Carter challenges the gender binary by de-victimizing “woman” and by engaging in a style of writing that overturns western culture’s definitions of “woman” Carter provides a version of Sleeping Beauty that radically differs from the hegemonic/patriarchal versions.

Each year liver cancer kills more than half a million people, making it the third leading cause of cancer-related death worldwide. Annual incidence continues to rise steadily, both domestically and globally, increasing the burden of this disease. Advancements in the ability to obtain detailed molecular profiles of tumors have led to the successful development of targeted therapies for a number of different cancers. Unfortunately, however, the molecular pathogenesis of liver cancer is poorly understood relative to many other types of malignancies. Thus, the identification of factors contributing to the development and progression of liver tumors is a major goal of current research. In pursuit of this goal, I have utilized the Sleeping Beauty (SB) transposon system as a tool for forward genetic mutagenesis screening in mice. The SB system recapitulates the kinetics of spontaneous tumor development in humans by providing a stepwise accumulation of mutations. Micro-evolutionary processes within a developing tumor lead to the selective expansion of cells harboring mutations that confer some kind of selective advantage. By identifying the most prevalent mutation events within a specific tumor type across a large number of independent samples, a list of genes implicated as being involved in tumorigenesis can be generated. Using this approach, the Dlk1-Dio3 imprinted domain was identified as a site of frequent mutation in SB-induced hepatocellular carcinomas (HCCs). I discovered that the mechanistic basis for recurrent selection of transposon insertion within this domain in liver tumors involved activated expression of Retrotransposon-like 1 (Rtl1). I also found that RTL1 activation is a common event in human HCC, suggesting that it could potentially be beneficial as a therapeutic target in a subset of patients. Etiological factors related to liver cancer development are varied, but are linked by the fact that each provides a chronic liver injury stimulus that promotes the development of hepatic fibrosis. In fact, ˜ 90% of human HCC occurs in this context, and yet the majority of mouse liver cancer models fail to account for this important environmental component of the disease. I have conducted a screen for genetic drivers of liver cancer in the presence or absence of hepatic fibrosis. Comparison of mutation profiles between fibrotic and non-fibrotic tumors revealed largely non-overlapping sets of candidate genes, indicative of a differential selective pressure for mutations depending on the fibrotic context of the liver. Driver mutations identified preferentially in the presence of liver fibrosis have a high likelihood of relevance to human disease, given the similarities in environmental context and kinetics of mutation acquisition. Consistent with this idea, multiple genes with well-established roles in human HCC were found to be preferentially mutated in SB-induced tumors developed in a fibrotic liver. Before a candidate cancer gene identified in an animal model system can have an impact on human disease, its proposed role in tumorigenesis must be validated. Existing techniques for validation of putative liver cancer genes suffer from significant limitations including high cost, low throughput, and a level of complexity that prohibits widespread utilization. I have contributed to the generation of a novel tool for in vivo validation of candidate genes that is not subject to these limitations. By combining elements of recombinant adenoviral vectors and the piggyBac transposition system, we have generated a highly flexible gene delivery system with significant advantages over existing techniques. The Ad-PB system has broad accessibility and applicability, making it a valuable tool for advancing efforts to improve cancer therapies.

Several philosophical problems are based on an analogy between a real situation and a probabilistic model. Such problems are based on urn analogies. The present dissertation aims to describe and implement a methodology oriented towards the resolution of philosophical problems based on an urn analogy. This methodology is based on the use of the n-universes. To this end, I describe first the n-universes in a detailed way. I also discuss the difficulties of the theory of n-universes related to the demultiplication of the criteria and to the relation one/many between the objects and a given criterion.On the one hand, I present an application of the framework of n-universes to the Doomsday argument and to the problems recently appeared in the literature in keeping with the Doomsday argument. My concern is also with showing how the application of the framework of n-universes to several problems and thought experiments related to the Doomsday argument helps clarifying the problem data and making disappear the associated ambiguity. I present then an analysis of the following problems related to the Doomsday argument: the two urn case, God's Coin Toss, the Sleeping Beauty Problem, the Presumptuous Philosopher, Lazy Adam, and the Shooting-Room Paradox. I present lastly a solution to the Doomsday argument, based on a third route, by contrast to two types of solutions classically described.On the other hand, I present an application of the framework of n-universes to Goodman's paradox. I replace first Goodman's statement in the framework of n-universes. I propose then a solution to the paradox, based on a distinction between two different modelizations of Goodman's statement in two structurally different n-universes.

Die Gentherapie hämatopoetischer Stammzellen (HSCs) besitzt das Potenzial, verschiedene erbliche, nur symptomatisch behandelbare, Erkrankungen dauerhaft zu heilen. Die Mehrheit der aktuell angewandten Verfahren dazu, basiert auf der Isolation von hämatopoetischen Stammzellen, der ex vivo Modifikation dieser Zellen durch retrovirale Vektoren und der Reinfusion der modifizierten Zellen in den immunsupprimierten Patienten. Dieser Ansatz ist mit einer Reihe von Nachteilen verbunden, unter anderem einem teilweisen Verlust des Rekonstitutionsvermögens der Stammzellen nach ex vivo Kultur oder der Gefahr der Transformation durch Integration des retroviralen Vektorgenoms. Darüber hinaus sind aktuelle Gentherapieansätze mit hohen Kosten und großem logistischem Aufwand verbunden, was den Zugang zu diesen Behandlungen für potentielle Patienten stark einschränkt. Die vorliegende Arbeit verfolgt einen neuen Ansatz zur Gentherapie von HSCs, der auf der Mobilisierung von Stammzellen aus dem Knochenmark in den peripheren Blutstrom und der Transduktion dieser Stammzellen mit adenoviralen Vektoren basiert. Hierbei codieren die Vektoren sowohl ein Transgen als auch eine Integrationsmaschinerie. Der erste Teil der Arbeit belegt in einem humanen CD46-transgenen Mausmodell, dass adenovirale Vektoren der ersten Generation in der Lage sind, mobilisierte HSCs im Blut zu transduzieren und dass es den so transduzierten Stammzellen möglich ist, zurück ins Knochenmark zu migrieren und dort das Transgen zu exprimieren. Allerdings wurde im Verlauf von zwei Wochen ein Rückgang der Transgenexpression beobachtet. Um dies zu umgehen, wurde ein adenovirales Vektorsystem der dritten Generation genutzt, das eine hochaktive Sleeping Beauty Transposase, zum Zweck der Transgenintegration, codiert. Dieses System ermöglichte die stabile Genmodifikation mobilisierter hämatopoetischer Stammzellen nach intravenöser Injektion. Die Expression des Transgens konnte über längere Zeitspannen (bis 12 Wochen) beobachtet werden. Die modifizeirten Stammzellen waren darüber hinaus in der Lage, genmodifizierte Kolonien in vitro zu bilden und das hämatopoetische System letal bestrahlter Mäuse nach Knochenmarkstransplantation zu rekonstituieren. Es wurde somit gezeigt, dass HSCs nach in vivo Modifikation weiterhin funktional waren. / The gene therapy of hematopoietic stem cells holds the potential for curative treatment of several otherwise incurable inherited diseases. The majority of current gene therapy treatments relies on the collection of hematopoietic stem cells, their ex vivo modification with retroviral vectors and their transplantation into a myeloconditioned patient. This approach entails several disadvantages, including a reduction of stem cell engraftment potential after ex vivo culture and the potential danger of integrational mutagenesis. In addition, the high costs and complex logistics of this approach limit the access of patients to gene therapeutic regimens. This work explores an alternative approach to hematopoietic stem cell (HSC) gene therapy, termed stem cell in vivo transduction. This approach is based on the mobilization of HSCs from the bone marrow into the peripheral blood and the transduction of the stem cells with adenoviral vectors delivering a transgene as well as a transgene integration machinery. In the first part of this work, it was shown that first-generation adenoviral vectors could be used for the transduction of mobilized HSCs in the periphery of human CD46-transgenic mice. Further, the transduced HSCs were able to home back to the bone marrow and express the transgene. However, over the course of 14 days, a loss of transgene expression in HSCs was observed. To ameliorate these shortcomings, helper-dependent adenoviral vectors encoding a hyperactive Sleeping Beauty transposase for transgene integration were used for stable gene modification of hematopoietic stem cells following intravenous vector administration in mobilized human CD46-transgenic mice. Using this improved vector platform, gene marking of bone marrow HSCs could be observed for extended periods of time (up to 12 weeks). Further, the functionality of the modified HSCs was demonstrated both in colony-forming progenitor assays as well as through the transplantation of gene-modified HSCs into lethally irradiated recipients. Transplantation of modified HSCsled to long-term multi-lineage reconstitution showing that gene-modified stem cells were fully functional. Subsequently the safety of systemic vector administration in mobilized hosts as well as of the Sleeping Beauty-mediated transgene integration was assessed in human CD46- transgenic mice. Lastly, the stem cell in vivo transduction approach was employed in NOG mice transplanted with human CD34+ cells, as well as in Macaca nemestrina non-human primates.

The Grimm Brothers’ Little Briar-Rose is a beloved fairytale, which is more commonly known as Sleeping Beauty. What began as a Volksmärchen, is now a world famous and beloved Kunstmärchen. The Brothers collected and adapted the tale, incorporating their own literary style, helping to develop a literary Germanic cultural history. In this thesis I analyze how the tale evolves from the original oral tale to the literary story, and how various perspectives of culture and authors, with particular audiences in mind, adapt their versions. Historical background of the Grimms and their influences, an analysis of how the story was revised by the Grimms in the 1812 and 1857 editions, how American children’s versions compare to the Grimms’ version and how Jane Yolen’s version of Sleeping Beauty meets the structural and cultural expectations of the Grimms’ tale are examined.

No description available.