Adeno-associated virus (AAV) consists of a simple genome, infects mammalian cells, displays nonpathogenicity in humans, and spans an array of serotypes and variants bearing distinct tissue tropisms. These attributes lend AAV tremendous promise as a gene delivery vector, further substantiated by its extensive testing in human clinical trials. Rational design approaches to capsid engineering leverage current scientific knowledge of AAV to further modulate, enhance and optimize the performance of the vectors. Capsid modification strategies include amino acid point mutations, peptide domain insertions, and chemical biology approaches. Through such efforts, insights regarding AAV capsid sequence-structure-function relationships can be learned. Developments over the last 5 years in rational design-based capsid engineering approaches will be presented and discussed.
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http://dx.doi.org/10.1016/j.cobme.2018.09.004 | DOI Listing |
Viruses
January 2025
Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai 200433, China.
This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and tag types in the VP1 capsid protein. The pseudovirus's infectivity and replication can be assessed by measuring postinfection luciferase signals.
View Article and Find Full Text PDFBiomedicines
January 2025
Kellogg Eye Center, Department of Ophthalmology and Visual Science, University of Michigan, Ann Arbor, MI 48105, USA.
Intraocular malignant tumors are rare; however, they can cause serious life-threatening complications. Uveal melanoma (UM) and retinoblastoma (RB) are the most common intraocular tumors in adults and children, respectively, and come with a great disease burden. For many years, several different treatment modalities for UM and RB have been proposed, with chemotherapy for RB cases and plaque radiation therapy for localized UM as first-line treatment options.
View Article and Find Full Text PDFVaccines (Basel)
January 2025
Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
Background/objectives: Conventional live oral poliovirus vaccines (OPVs) effectively prevent poliomyelitis. These vaccines are derived from three attenuated Sabin strains of poliovirus, which can revert within the first week of replication to a neurovirulent phenotype, leading to sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccinees and their contacts. A novel OPV2 vaccine (nOPV2) with enhanced genetic stability was developed recently; type 1 and type 3 nOPV strains were engineered using the nOPV2 genome as a backbone by replacing the capsid precursor polyprotein (P1) with that of Sabin strains type 1 and type 3, respectively.
View Article and Find Full Text PDFHum Gene Ther
January 2025
Department of Internal Medicine V, University Hospital Schleswig-Holstein and University of Kiel, Kiel, Germany.
Adeno-associated viral (AAV) vectors are increasingly used for preclinical and clinical cardiac gene therapy approaches. However, gene transfer to cardiomyocytes poses a challenge due to differences between AAV serotypes in terms of expression efficiency and . For example, AAV9 vectors work well in rodent heart muscle cells but not in cultivated neonatal rat ventricular cardiomyocytes (NRVCMs), necessitating the use of AAV6 vectors for studies.
View Article and Find Full Text PDFJ Virol
January 2025
Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, USA.
Human astroviruses (HAstVs) are a leading cause of viral childhood diarrhea that infects nearly every individual during their lifetime. Although human astroviruses are highly prevalent, no approved vaccine currently exists. Antibody responses appear to play an important role in protection from HAstV infection; however, knowledge about the neutralizing epitope landscape is lacking, as only three neutralizing antibody epitopes have previously been determined.
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