Perinatal Gene Transfer to the Liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer

Off-shell supergravity-matter couplings in three dimensions

We develop the superspace geometry of N-extended conformal supergravity in three space-time dimensions. General off-shell supergravity-matter couplings are constructed in the cases N=1,2,3,4.Comment: 73 pages; V5: typos in eqs. (3.4b), (3.17) and (4.24) correcte

Six-dimensional Supergravity and Projective Superfields

We propose a superspace formulation of N=(1,0) conformal supergravity in six dimensions. The corresponding superspace constraints are invariant under super-Weyl transformations generated by a real scalar parameter. The known variant Weyl super-multiplet is recovered by coupling the geometry to a super-3-form tensor multiplet. Isotwistor variables are introduced and used to define projective superfields. We formulate a locally supersymmetric and super-Weyl invariant action principle in projective superspace. Some families of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3), (2.14b), (2.16) and (2.17) correcte

Goldstinos, Supercurrents and Metastable SUSY Breaking in N=2 Supersymmetric Gauge Theories

We construct an N=2 supersymmetric generalization of the N=1 supercurrent formalism of Komargodski and Seiberg (KS) and use it to show that N=2 theories with linear superconformal anomalies cannot break SUSY under certain broad assumptions. This result suggests that there are no metastable SUSY breaking vacua in a large class of theories that includes N=2 Super Yang-Mills (SYM).Comment: 19 pages; minor revisions; JHEP versio

Three-dimensional (p,q) AdS superspaces and matter couplings

We introduce N-extended (p,q) AdS superspaces in three space-time dimensions, with p+q=N and p>=q, and analyse their geometry. We show that all (p,q) AdS superspaces with X^{IJKL}=0 are conformally flat. Nonlinear sigma-models with (p,q) AdS supersymmetry exist for p+q4 the target space geometries are highly restricted). Here we concentrate on studying off-shell N=3 supersymmetric sigma-models in AdS_3. For each of the cases (3,0) and (2,1), we give three different realisations of the supersymmetric action. We show that (3,0) AdS supersymmetry requires the sigma-model to be superconformal, and hence the corresponding target space is a hyperkahler cone. In the case of (2,1) AdS supersymmetry, the sigma-model target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations of the two-sphere of complex structures.Comment: 52 pages; V3: minor corrections, version published in JHE

N=2 supergravity and supercurrents

We address the problem of classifying all N=2 supercurrent multiplets in four space-time dimensions. For this purpose we consider the minimal formulation of N=2 Poincare supergravity with a tensor compensator, and derive its linearized action in terms of three N=2 off-shell multiplets: an unconstrained scalar superfield, a vector multiplet, and a tensor multiplet. Such an action was ruled out to exist in the past. Using the action constructed, one can derive other models for linearized N=2 supergravity by applying N=2 superfield duality transformations. The action depends parametrically on a constant non-vanishing real isotriplet g^{ij}=g^{ji} which originates as an expectation value of the tensor compensator. Upon reduction to N=1 superfields, we show that the model describes two dually equivalent formulations for the massless multiplet (1,3/2)+(3/2,2) depending on a choice of g^{ij}. In the case g^{11}=g^{22}=0, the action describes (i) new minimal N=1 supergravity; and (ii) the Fradkin-Vasiliev-de Wit-van Holten gravitino multiplet. In the case g^{12}=0, on the other hand, the action describes (i) old minimal N=1 supergravity; and (ii) the Ogievetsky-Sokatchev gravitino multiplet.Comment: 40 pages; v2: added references, some comments, new appendi

D=3, N=8 conformal supergravity and the Dragon window

We give a superspace description of D=3, N=8 supergravity. The formulation is off-shell in the sense that the equations of motion are not implied by the superspace constraints (but an action principle is not given). The multiplet structure is unconventional, which we connect to the existence of a "Dragon window", that is modules occurring in the supercurvature but not in the supertorsion. According to Dragon's theorem this cannot happen above three dimensions. We clarify the relevance of this window for going on the conformal shell, and discuss some aspects of coupling to conformal matter.Comment: plain tex, 24 pp v2: minor change

Extended supersymmetric sigma models in AdS_4 from projective superspace

There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We also develop a novel description of the most general N=2 supersymmetric nonlinear sigma-model in AdS_4 in terms of chiral superfields on three-dimensional N=2 flat superspace without central charge. This superspace naturally originates from a conformally flat realization for the four-dimensional N=2 AdS superspace that makes use of Poincare coordinates for AdS_4. This novel formulation allows us to uncover several interesting geometric results.Comment: 88 pages; v3: typos corrected, version published in JHE

N=2 Conformal Superspace in Four Dimensions

We develop the geometry of four dimensional N=2 superspace where the entire conformal algebra of SU(2,2|2) is realized linearly in the structure group rather than just the SL(2,C) x U(2)_R subgroup of Lorentz and R-symmetries, extending to N=2 our prior result for N=1 superspace. This formulation explicitly lifts to superspace the existing methods of the N=2 superconformal tensor calculus; at the same time the geometry, when degauged to SL(2,C) x U(2)_R, reproduces the existing formulation of N=2 conformal supergravity constructed by Howe.Comment: 43 pages; v2 references added, acknowledgments update

N=8 Counterterms and E7(7) Current Conservation

We examine conservation of the E7(7) Noether-Gaillard-Zumino current in the presence of N=8 supergravity counterterms using the momentum space helicity formalism, which significantly simplifies the calculations. The main result is that the 4-point counterterms at any loop order L are forbidden by the E7(7) current conservation identity. We also clarify the relation between linearized and full non-linear superinvariants as candidate counterterms. This enables us to show that all n-point counterterms at L=7, 8 are forbidden since they provide a non-linear completions of the 4-point ones. This supports and exemplifies our general proof in arXiv:1103.4115 of perturbative UV finiteness of N=8 supergravity.Comment: 18 page