6,679 research outputs found
The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases
Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Here, we review the advances in non-viral gene augmentation strategies, such as the use of plasmids with minimal bacterial backbones and scaffold/matrix attachment region (S/MAR) sequences, that have the capability to overcome these weaknesses by accommodating genes of any size and maintaining episomal transgene expression with a lower risk of eliciting an immune response. Low retinal transfection rates remain a limitation, but various strategies, including coupling the DNA with different types of chemical vehicles (nanoparticles) and the use of electrical methods such as iontophoresis and electrotransfection to aid cell entry, have shown promise in preclinical studies. Non-viral gene therapy may offer a safer and effective option for future treatment of IRDs
USH2A-retinopathy: From genetics to therapeutics
Bilallelic variants in the USH2A gene can cause Usher syndrome type 2 and non-syndromic retinitis pigmentosa. In both disorders, the retinal phenotype involves progressive rod photoreceptor loss resulting in nyctalopia and a constricted visual field, followed by subsequent cone degeneration, leading to the loss of central vision and severe visual impairment. The USH2A gene raises many challenges for researchers and clinicians due to a broad spectrum of mutations, a large gene size hampering gene therapy development and limited knowledge on its pathogenicity. Patients with Usher type 2 may benefit from hearing aids or cochlear implants to correct their hearing defects, but there are currently no approved treatments available for the USH2A-retinopathy. Several treatment strategies, including antisense oligonucleotides and translational readthrough inducing drugs, have shown therapeutic promise in preclinical studies. Further understanding of the pathogenesis and natural history of USH2A-related disorders is required to develop innovative treatments and design clinical trials based on reliable outcome measures. The present review will discuss the current knowledge about USH2A, the emerging therapeutics and existing challenges
A Minimalist Turbulent Boundary Layer Model
We introduce an elementary model of a turbulent boundary layer over a flat
surface, given as a vertical random distribution of spanwise Lamb-Oseen vortex
configurations placed over a non-slip boundary condition line. We are able to
reproduce several important features of realistic flows, such as the viscous
and logarithmic boundary sublayers, and the general behavior of the first
statistical moments (turbulent intensity, skewness and flatness) of the
streamwise velocity fluctuations. As an application, we advance some heuristic
considerations on the boundary layer underlying kinematics that could be
associated with the phenomenon of drag reduction by polymers, finding a
suggestive support from its experimental signatures.Comment: 5 pages, 10 figure
Bose-Einstein condensation for interacting scalar fields in curved spacetime
We consider the model of self-interacting complex scalar fields with a rigid
gauge invariance under an arbitrary gauge group . In order to analyze the
phenomenon of Bose-Einstein condensation finite temperature and the possibility
of a finite background charge is included. Different approaches to derive the
relevant high-temperature behaviour of the theory are presented.Comment: 28 pages, LaTe
There is no new physics in the multiplicative anomaly
We discuss the role of the multiplicative anomaly for a complex scalar field
at finite temperature and density. It is argued that physical considerations
must be applied to determine which of the many possible expressions for the
effective action obtained by the functional integral method is correct. This is
done by first studying the non-relativistic field where the thermodynamic
potential is well-known. The relativistic case is also considered. We emphasize
that the role of the multiplicative anomaly is not to lead to new physics, but
rather to preserve the equality among the various expressions for the effective
action.Comment: 24 pages, RevTex, no figure
One-Loop Renormalization of a Self-Interacting Scalar Field in Nonsimply Connected Spacetimes
Using the effective potential, we study the one-loop renormalization of a
massive self-interacting scalar field at finite temperature in flat manifolds
with one or more compactified spatial dimensions. We prove that, owing to the
compactification and finite temperature, the renormalized physical parameters
of the theory (mass and coupling constant) acquire thermal and topological
contributions. In the case of one compactified spatial dimension at finite
temperature, we find that the corrections to the mass are positive, but those
to the coupling constant are negative. We discuss the possibility of
triviality, i.e. that the renormalized coupling constant goes to zero at some
temperature or at some radius of the compactified spatial dimension.Comment: 16 pages, plain LATE
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