HPV VLP(Optipharm)

Virus-like particles (VLPs) show considerable potential for a wide array of therapeutic applications, spanning from vaccines targeting infectious diseases to applications in cancer immunotherapy and drug delivery. In the context of hepatitis B core antigen (HBcAg) VLPs, a promising candidate for gene delivery approaches, the naturally occurring nucleic acid (NA) binding region is commonly utilized for effective binding of various types of therapeutic nucleic acids (NAther). During formation of the HBcAg VLPs, host cell-derived nucleic acids (NAhc) might be associated to the NA binding region, and are thus encapsulated into the VLPs. Following a VLP harvest, the NAhc need to be removed effectively before loading the VLP with NAther. Various techniques reported in literature for this NAhc removal, including enzymatic treatments, alkaline treatment, and lithium chloride precipitation, lack quantitative evidence of sufficient NAhc removal accompanied by a subsequent high VLP protein recovery. In this study, we present a novel heparin chromatography-based process for effective NAhc removal from HBcAg VLPs. Six HBcAg VLP constructs with varying lengths of the NA binding region and diverse NAhc loadings were subjected to evaluation. Process performance was thoroughly examined through NAhc removal and VLP protein recovery analyses. Hereby, reversed phase chromatography combined with UV/Vis spectroscopy, as well as silica spin column-based chromatography coupled with dye-based fluorescence assay were employed. Additionally, alternative process variants, comprising sulfate chromatography and additional nuclease treatments, were investigated. Comparative analyses were conducted with LiCl precipitation and alkaline treatment procedures to ascertain the efficacy of the newly developed chromatography-based methods. Results revealed the superior performance of the heparin chromatography procedure in achieving high NAhc removal and concurrent VLP protein recovery. Furthermore, nuanced relationships between NA binding region length and NAhc removal efficiency were elucidated. Hereby, the construct Cp157 surpassed the other constructs in the heparin process by demonstrating high NAhc removal and VLP protein recovery. Among the other process variants minimal performance variations were observed for the selected constructs Cp157 and Cp183. However, the heparin chromatography-based process consistently outperformed other methods, underscoring its superiority in NAhc removal and VLP protein recovery.

Background/Objectives: The treatment of periarticular distal radius fractures remains challenging. Different surgical treatment options have been proposed as alternatives to conservative treatment. This systematic review aims to compare the functional outcomes, radiological outcomes, and complications among volar locking plates (VLPs), Kirschner-wire fixations, and external fixations (EFs) for distal radius fractures in patients aged 60 years and older. Methods: We conducted a comprehensive search of PubMed, Cochrane, and Science Direct databases assessing the effects of VLP, EF, and K-wire treatments for distal radius fractures in patients aged 60 years and over. The primary outcome was the evaluation of the range of motion (ROM) degrees after three surgical procedures, trying to assess the best treatment option. The secondary outcome included evaluation of the Disabilities of the Arm, Shoulder, and Hand (DASH) score, quick-DASH score, Patient-Rated Wrist Evaluation (PRWE) score, Visual Analog Scale (VAS) score, grip strength, radiographic assessment, and complications comparing VLPs, EFs and K-wires. Results: A total of 23 studies were included, comparing VLP, EF, and K-wire fixation. The overall population comprised 5618 patients, with 4690 females and 1015 males, of which 4468 patients were treated with VLP, 503 with EF, and 647 with K-wire. The most common complications among the VLP group were complex regional pain syndrome (7.5%) and carpal tunnel syndrome (6.8%); for the EF group, infections (9.8%) and carpal tunnel syndrome (6.8%); and for the K-wire group, carpal tunnel syndrome (7.5%) and infections (6.9%). Conclusions: VLP showed better clinical outcomes in the first few months after treatment. However, these differences decreased over time and became similar after one year. EF and K-wire fixations remain easier to manage during surgery.