China
Africa
Explore chapters and articles related to this topic
Order Piccovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Furthermore, the random peptide libraries were displayed on the AAV2 vector to select for targeted gene therapy vectors on specific cells (Müller et al. 2003; Waterkamp et al. 2006; Naumer et al. 2012a, b). Adachi and Nakai (2010) engineered a novel peptide display library platform based on the AAV1 virion with aa 445–568 being replaced with those of AAV9 in order to impair infectivity and delay blood clearance. The insect cells-produced AAV2 VLPs were coated with polyethyleneimine to ensure efficient siRNA delivery in breast cancer therapy (Shao et al. 2012). Lee NC et al. (2012) improved axial muscle tropism and decreased liver tropism by insertion of acidic six aspartic acids D6 oligopeptide into heparan sulfate proteoglycan binding region within the AAV2 VP1. Kienle et al. (2012) generated the synthetic AAV vectors by DNA shuffling. The targeting to the cancer cell-surface marker EGFR was improved by fusion of two modular targeting molecules (DARPin or Affibody) to N-terminus of the AAV2 VP2 (Hagen et al. 2014). Pandya et al. (2014) ensured the specific targeting to dendritic cells by mutational modification of the surface of the AAV6 vector. The visualization of the AAV vectors was achieved by replacement of VP2 by the VP2 with N-terminally fused eGFP protein (Lux et al. 2005).
The Emerging Role of Exosome Nanoparticles in Regenerative Medicine
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Zahra Sadat Hashemi, Mahlegha Ghavami, Saeed Khalili, Seyed Morteza Naghib
Bioengineering of exosomes to introduce targeting ligands: For specific targeting of exosomes, two strategies are developed: (1) parental cell engineering: As already discussed, exosomes are packaged by a lipid bilayer with distinct surface markers like CD9, CD63, and CD81. One of the most efficient strategies for introducing ligands on the surface of exosome is the expression of ligand with a fusion protein abundantly expressed in the exosomes. In this method, the parent cells were genetically modified with DNA encoding a ligand (or a receptor), which is specified for a receptor (or a ligand). Therefore, the secretion of parent cell-derived exosomes expressing the targeting peptide would be occurred. For instance, Gomari and colleagues transfected HEK293T cell lines with pLEX-LAMP2b-DARPin vector. The condition media containing viral particles was collected. The MSCs as a preference source of exosomes were transduced by these lenti viral particles. The LAMP2b-DARPin MSC-derived exosomes were harvested, which are effectively targeting HER2-positive breast tumour mice models (Gomari et al. 2019). (2) Post-isolation engineering: It is also known as post-insertion modification. In this procedure, the naive purified EVs were incubated with modified surface proteins that result in surface modification of EVs (Hood 2016; Kooijmans et al. 2016). Two methods of directed-EVs generation are compared by Wang et al. (Wang et al. 2018a). In this study, the HEK293 cells were transfected by pEVC1C2HER plasmid that codes for EVHB (anti-HER2 scFv antibody). The transfected HEK293-derived exosomes were obtained (called transfection EVs). In another experiment, the intact HEK293 cell-derived exosomes were harvested and incubated with pure EVHB (called reconstitution EVs). The ELISA results have showed that in comparison to transfection EVs, tenfold higher amount of the reconstitution EVs were bound to the HER2 receptor. Loading-modified exosomes with therapeutics that stimulate the regeneration capacity towards injured cells and tissues would be a promising strategy in regenerative therapy.
Abicipar pegol for neovascular age-related macular degeneration
Published in Expert Opinion on Biological Therapy, 2020
Rehan M. Hussain, Christina Y. Weng, Charles C. Wykoff, Raya A. Gandhi, Seenu M. Hariprasad
Abicipar pegol (Allergan, Dublin, Ireland) is a DARPin® (Designed Ankyrin Repeat Protein, a registered trademark of Molecular Partners AG, Switzerland)-based anti-VEGF drug being evaluated for the treatment of nAMD. DARPin therapeutics are a class of small proteins derived from natural ankyrin repeat proteins, which bind to a single target with a high degree of specificity and affinity, allowing them to be active at lower concentrations. As their molecular size is smaller than that of antibodies, they may have better tissue penetration and a longer duration of effect [18,43]. DARPins serve as potential therapeutics for a number of indications in oncology, ophthalmology, human immunodeficiency virus, and allergic reactions including allergic asthma [44,45]. Box 1 summarizes the key data about abicipar pegol.
Abicipar pegol: an investigational anti-VEGF agent for the treatment of wet age-related macular degeneration
Published in Expert Opinion on Investigational Drugs, 2020
Lorenzo Ferro Desideri, Carlo Enrico Traverso, Massimo Nicolò
Abicipar pegol belongs to the DARPin family, encompassing several ankyrin repeat proteins including human Ankyrin or human GA-binding protein [29]. DARPins are small, single-domain proteins (14 − 21 kDa), which is almost one-third of the size of Fab fragment, representing currently the smallest antibody fragment approved as a therapeutic agent [30]. In particular, DARPin proteins are characterized by high affinity-binding and selectivity, likely due to their molecular property to minimize free entropy while binding the target, as opposed to antibody activity, in which there are flexible hypervariable loops intercalating with the antigen [31]. In fact, their binding affinity typically fits in the picomolar range [29]. In addition, molecular studies have shown DARPin proteins high thermodynamic stability and high solubility, leading to the possibility to develop high-concentration formulations [32].
Brolucizumab: an evolution in treatment for neovascular age-related macular degeneration
Published in Expert Review of Ophthalmology, 2020
Ee Lin Ong, Kimberly Spooner, Thomas Hong, Andrew Chang
Abicipar pegol is a 34 kDa designed ankyrin repeat protein (DARPin) molecule with anti-VEGF properties [61,62]. DARPin molecules are small proteins designed to bind to their targets with high specificity and affinity [63], allowing a high molar dose which in theory should allow for better tissue penetration and less frequent dosing. In comparison to currently available anti-VEGF treatment options, 2.0 mg of Abicipar is equivalent to approximately 3–4 times the aflibercept 2.0 mg dose and 5.6 times the 0.5 mg ranibizumab dose in terms of molar concentration. In CEDAR and SEQUOIA [64,65], two Phase III randomized clinical studies of patients with nAMD, abicipar pegol treatment was compared to ranibizumab. Abicipar pegol was administered in both 8- and 12-week schedules and was non-inferior to monthly ranibizumab.