Gene delivery to the myocardium by intrapericardial injection

Abstract

Several studies have demonstrated the feasibility of gene cardium. Transgene expression is predominant in the left transfer into the heart muscle. However, all the available ventricle and the interventricular septum but limited in the data also indicate that the extent of transfection remains right ventricle. In vivo echocardiographic measurements of limited. As an alternative method to intravascular administhe left ventricular diameters at end diastolic and end systration, we have developed a novel strategy which uses tolic times show no difference between virus-and shamthe pericardial sac. When a replication-deficient adenovirus injected animals, thus indicating a good clinical tolerance containing the cDNA encoding a bacterial ␤-galactosidase to this strategy of virus delivery. The same protocol has is injected into the pericardial sac of adult Wistar rats the been used with the same efficiency in mice, which leads staining is exclusively restricted to the pericardial cell layus to propose injection into the pericardial sac as an effecers. However, injecting a mixture of collagenase and hyalutive and harmless method for gene transfer into the heart ronidase together with the virus, leads to a large diffusion muscle. of the transgene activity, reaching up to 40% of the myo-

Targeted Modification of Atrial Electrophysiology by Homogeneous Transmural Atrial Gene Transfer

“…A conclusion from those studies was that pronase and subtilisin cleaved the receptor and prevented virus attachment, whereas trypsin and chymotrypsin cleaved other surface proteins, thus improving access to the receptor. Fromes et al 23 extended those findings by including collagenase and hyaluronidase in gene transfer solutions injected into the pericardial space of rats. They observed patchy gene transfer to the ventricular epicardium and to some myocytes penetrating to a depth of roughly half the thickness of the ventricular myocardium.…”

Hyaluronidase enhances recombinant adeno-associated virus (rAAV)-mediated gene transfer in the rat skeletal muscle

“…The fact that in vitro transduction of Hela cells with rAAVnlsLacZ was not modified by preincubation with hyaluronidase (data not shown), suggests that the enzyme may not act at the cellular level (for example by enhancing AAV entry into the cells) but rather through extracellular matrix dissociation enhancing vector diffusion in the tissue. Although Fromes et al 10 recently reported that hyaluronidase alone was ineffective in facilitating adenovirus-mediated gene transfer to the myocardium across the pericardial barrier, a mix of collagenase and hyaluronidase was found to enhance the diffusion of the recombinant adenovirus. Altogether, these observations indicate that hyaluronidase treatment may be important to enhance rAAV muscle diffusion and transduction in larger animals, such as non-human primates in which transduction rates are limited by the avaibility of high-titer rAAV.…”

Hepatic PCSK9 Expression Is Regulated by Nutritional Status via Insulin and Sterol Regulatory Element-binding Protein 1c

“…Both adenovirus vectors containing the transcriptionally active N-terminal fragment (amino acids 1-403) of SREBP-1c (AdSREBP-1c, 6 plaque-forming units/cell) and the dominant negative form of SREBP-1 (AdSREBP-1cDN, 15 plaque-forming units/cell) were generous gifts from Dr. Foufelle (INSERM U465, Paris, France) and have been described previously (30) (18). Sham control vector (Adnul) was generated by the Vector Core of the University Hospital of Nantes (38). T0901317 (Sigma) was dissolved with Me 2 SO.…”