Cryo-EM Structure of Adeno-associated virus-4 at 2.2 Å resolution

Adeno-associated virus (AAV) is the vector of choice for several approved gene therapy treatments and is the basis for many ongoing clinical trials. Various strains of AAV exist (referred to as serotypes), each with their own transfection characteristics. Here, we present a high-resolution cryo-electron microscopy structure (2.2 Å) for AAV serotype 4 (AAV4). The receptor responsible for transduction of the AAV4 clade of AAV viruses (including AAV11, 12 and rh32.33) is unknown. Other AAVs interact with the same cell receptor, Adeno-associated virus receptor (AAVR), in one of two different ways. AAV5-like viruses interact exclusively with the polycystic kidney disease-like [PKD]-1 domain of AAVR while most other AAVs interact primarily with the PKD2 domain. A comparison of the present AAV4 structure with prior corresponding structures of AAV5, AAV2 and AAV1 in complex with AAVR, provides a foundation for understanding why the AAV4-like clade is unable to interact with either PKD1 or PKD2. The conformation of the AAV4 capsid in variable regions I, III, IV and V on the viral surface appears to be sufficiently different from AAV2 to ablate binding with PKD2. Differences between AAV4 and AAV5 in variable region VII appear sufficient to exclude binding with PKD1.

Arterial Embolization of Polycystic Kidneys for Heterotopic Transplantation

Introduction: The purpose of this study was to evaluate the efficacy of polycystic kidney embolization, performed to reduce kidney volume before heterotopic kidney transplantation, as this technique could be an alternative to pretransplant nephrectomy. Materials and Methods: All patients who underwent pretransplant embolization of polycystic kidneys were included in a prospective register from June 2014 to February 2020. All patients underwent computed tomography (CT) scan with volumetric reconstruction (OsiriX, Bernex, Switzerland) before embolization and were then followed up at 3 and 6 months after embolization. Primary outcome was percentage of kidney volume reduction. Secondary outcomes were 30 day mortality and morbidity. Results: Thirty-one embolizations performed on 29 patients (medium age = 55.6; 62.1% male) were included between June 2014 and February 2020. All patients were under dialysis before embolization (9 peritoneal dialysis and 20 hemodialysis). Technical success was observed in 96.8% of cases. Mean procedural time was 65 minutes (range = 35–106 minutes) and mean length of in-hospital stay was 3.8 days (range = 3–6 days). A volume reduction allowing a kidney transplant was obtained for 28 patients (96.5%). The mean volume reduction was 39.9% (range = 6.01–68.2). The main observed complication was postembolization pain in 10 cases (32.2%). One patient needed complementary nephrectomy due to insufficient volume reduction. Twenty-three patients (79.3%) received renal transplant during follow-up with a mean delay of 19.5 month (range = 4–54). Conclusion: Polycystic kidney embolization is an effective and safe minimally invasive technique. It can be proposed as the first-choice technique for kidney transplant recipients as an alternative to pretransplantation nephrectomy.