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Related Concept Videos

Viral Structure00:56

Viral Structure

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Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
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Maxam-Gilbert Sequencing01:05

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In the same year as the discovery of the Sanger sequencing method, another group of scientists, Allan Maxam and Walter Gilbert, demonstrated their chemical-cleavage method for DNA sequencing. The Maxam-Gilbert method relies on using different chemicals that can cleave the DNA sequence at specific sites, the separation of resulting DNA fragments of variable size using electrophoresis, and deciphering the DNA sequence from the resulting gel bands.
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Related Experiment Video

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Isolation of Next-Generation Gene Therapy Vectors through Engineering, Barcoding, and Screening of Adeno-Associated Virus AAV Capsid Variants
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AAV capsid design: A Goldilocks challenge.

S Zolotukhin1, L H Vandenberghe2

  • 1Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.

Trends in Molecular Medicine
|January 30, 2022
PubMed
Summary

Adeno-associated virus (AAV) vectors are key for gene therapy medicines. Engineering AAV capsids improves targeting, safety, and endurance for effective gene delivery and treatment.

Keywords:
adeno-associated virus vectordirected evolutiongene therapymachine learning

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Area of Science:

  • * Gene therapy
  • * Virology
  • * Molecular biology

Background:

  • * In vivo therapeutic gene transfer represents a novel class of medicines.
  • * Adeno-associated virus (AAV) vectors are a preferred gene delivery vehicle for therapeutic gene expression.
  • * Safe and effective delivery of genetic cargo is crucial for gene therapy feasibility.

Purpose of the Study:

  • * To review recent trends in adeno-associated virus (AAV) capsid engineering.
  • * To highlight advancements in enhancing AAV targeting specificity, safety, and endurance.
  • * To discuss the challenges and strategies in developing multi-attribute AAV capsids.

Main Methods:

  • * Utilizing virion structure and phylogenetics for capsid design.
  • * Employing directed evolution techniques to generate novel capsid variants.
  • * Applying sequence analyses and machine learning for attribute optimization.

Main Results:

  • * Development of engineered AAV capsid variants with improved characteristics.
  • * Demonstrated potential for enhanced targeting specificity, safety, and endurance.
  • * Overcoming engineering challenges in combining multiple desirable traits into single capsids.

Conclusions:

  • * AAV capsid engineering is critical for advancing safe and enduring gene therapy.
  • * Integrated approaches combining structural, evolutionary, and computational methods are effective.
  • * Novel AAV variants hold promise for improved clinical applications of gene therapy.