Superselective endovascular tissue access using trans‐vessel wall technique: feasibility study for treatment applications in heart, pancreas and kidney in swine

Grankvist, Rikard; Jensen‐Urstad, Mats; Clarke, Jonathan; Lehtinen, Markku; Little, Philip; Lundberg, Johan; Arnberg, Fabian; Jönsson, Stefan; Chien, Kenneth R.; Holmin, Staffan

doi:10.1111/joim.12841

Cited by 7 publications

(10 citation statements)

References 28 publications

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“…administration enables efficient hepatic expression of mRNA cargos with subsequent therapeutic levels of protein (Supplementary Table 1). However, targeting of most organs other than liver requires improved delivery systems, whether directly via catheters 146 or by engineering of packaging systems with appropriate tropism. Every organ has its own advantages and obstacles for efficient delivery.…”

Section: Tissue Targetingmentioning

confidence: 99%

“…Trans-vessel-wall microcatheters can inject cells and other therapeutic agents directly into the tissue, increasing efficacy and decreasing the risk of adverse events 173 . Preclinical studies with this endovascular device show that it can directly access target tissues, such as the heart, kidney and pancreas, without the need to seal the puncture site 146 . Re-circulation devices, which allow the agent to pass the area of interest multiple times, can enhance transduction efficiency in large animal models 174 .…”

Section: Catheter Deliverymentioning

confidence: 99%

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Unlocking the promise of mRNA therapeutics

et al. 2022

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z and enhanced catalysis to the ribosomal complex [32][33][34][35][36] . Optimization of the poly(A) tail length (100-300 nucleotides) has proven critical in balancing the synthetic capability of a given mRNA 34,36 . Similarly, improved 5′ cap analogs not only increase translational capacity but also enhance capping efficiency, from 70% to 95%, greatly improving the in vitro transcription process 32,37 . The composition of the 3′ and 5′ UTRs can also be customized for the target cell of interest, increasing the efficiency and tissue specificity of translation 35,38,39 .At present, most mRNA products contain a synthetic UTR sequence from α-globin or β-globin [38][39][40] , but UTR optimization can further improve protein expression by a few fold 41,42 . Careful screening and customization to the target of interest could conceivably offer a wide range of improvements in future UTR sequences, allowing each mRNA to be tailored to the targeted cell and disease-induced microenvironment to maximize protein synthesis per mRNA transcript [41][42][43][44] .Perhaps the most critical advances in mRNA vaccines and therapeutics lie in the discovery that the inclusion of chemically modified nucleosides, particularly in uridine moieties, can markedly increase protein expression after in vitro or in vivo transfection. The chemical modifications of most new RNA formulations to date have been central in intellectual property claims 45,46 . Thus far, over 130 different naturally occurring chemical modifications of RNA have been reported 47,48 . The interest in methylpseudouridine and other modified nucleosides centers on their capacity to greatly reduce (up to 100-fold) detection by the Toll-like receptors of the innate immune system, resulting in an increase in protein expression in vivo compared to unmodified mRNA 40,[49][50][51][52][53] . Combinations of different types of chemical modifications, carriers, for the treatment of chronic conditions. The fifth section provides a comprehensive table and summary of current clinical trends in mRNA therapeutics. Finally, the sixth section considers the scope of mRNA therapeutics and guiding principles for near-term and longer-term clinical development of this novel therapeutic modality.

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Section: Tissue Targetingmentioning

confidence: 99%

Section: Catheter Deliverymentioning

confidence: 99%

Unlocking the promise of mRNA therapeutics

et al. 2022

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“…The field of gene therapy is gaining traction with the apparent success of therapies targeting hematopoietic stem cells, cancers and inherited muscular diseases [46,47]. Current gene therapies have focused on intravenous delivery of adenoassociated viral vectors that incorporate into cells Grankvist et al [32] to cause expression of the implanted genes. Just as with cell transplantation, however, there are other promising vectors of gene delivery that may not be able to transmigrate efficiently, or distribute in the body in a suboptimal way for some applications.…”

Section: What To Deliver?mentioning

confidence: 99%

“…Over the course of the previous studies, the authors noted that bleeding was exceedingly rare, even in occasional circumstances where prototype detachment failed and the device would be withdrawn without sealing the vessel wall puncture. Therefore, a modified prototype has now been designed and tested for trans‐vessel wall access without the requirements of a detachment zone, applicable in transvenous settings and in organs where very small haemorrhages would not be of consequence, should they occur despite the design for minimizing this risk . This is partly attributed to a new tip configuration requiring significantly less force to penetrate the vessel wall and an improved depth‐limiting collar design.…”

Section: The Trans‐vessel Wall Techniquementioning

confidence: 99%

The creation of an endovascular exit through the vessel wall using a minimally invasive working channel in order to reach all human organs

2019

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Since the establishment of the Seldinger technique for secure entry to the vascular system, there has been a rapid evolution in imaging and catheters that has made the arteries and veins internal routes to any place in the body for interventions. It is curious that a general exit from the vasculature in a similar manner has not been proposed earlier. Possibly, the simplest reason is that accidental perforation of the vasculature by guide wire or catheter is a feared adverse event in endovascular intervention. Most places in the body can be reached by ultrasonography or computed tomography‐guided intervention. Some organs such as the central nervous system, the heart and pancreas are harder to access and, in some organs, like the kidney, repeated percutaneous punctions to cover large areas is not suitable. We present a new general purpose micro‐endovascular device creating a working channel to these ‘hard to reach’ organs by an inverted Seldinger technique. This review details this trans‐vessel wall technique, which has been studied in pancreas for transplantation of insulin‐producing cells, for injection of contrast agent to the heart and to the brain, bowels and kidney in rat, rabbit, swine and macaque monkeys with up to one year of follow‐up without adverse events. Furthermore, the payloads that can be given through such a system are briefly discussed. Drugs, cells, gene vectors and other therapeutic substances may be injected directly to the tissue to increase efficacy and decrease risk of off‐site adverse effects.

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“…In the article accompanying this editorial, Grankvist and colleagues describe the use of an elegant trans‐vessel wall technique in an animal model for selective endovascular tissue access to the kidney, pancreas and heart. The potential diagnostic implications of this method are obvious: as noted in the article's discussion, interventionists will gain access to a less invasive technique that can facilitate tissue acquisition from difficult‐to‐reach sites, such as the pancreas.…”

mentioning

confidence: 99%