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Related Concept Videos

Conjugated Proteins02:50

Conjugated Proteins

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Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
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Conjugation01:19

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Conjugation is a form of horizontal gene transfer that primarily occurs in bacteria and some archaea, promoting genetic diversity and adaptation. Bacteria can acquire resistance genes through conjugative plasmids, allowing them to survive antibiotic treatments that would otherwise be lethal. This process involves direct contact between cells through specialized structures such as the sex pilus and is mediated by conjugative plasmids, including the F (fertility) factor.Conjugation requires...
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Bacterial conjugation is a mechanism of horizontal gene transfer that enables the exchange of genetic material between bacterial cells through direct contact. This process is facilitated by a donor cell carrying a conjugative plasmid, which encodes genes necessary for pilus formation, DNA replication, and transfer. The conjugative plasmid plays a central role in initiating and executing the transfer of genetic material.The tra region of the conjugative plasmid encodes proteins responsible for...
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Relative Strengths of Conjugate Acid-Base Pairs02:29

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Brønsted-Lowry acid-base chemistry is the transfer of protons; thus, logic suggests a relation between the relative strengths of conjugate acid-base pairs. The strength of an acid or base is quantified in its ionization constant, Ka or Kb, which represents the extent of the acid or base ionization reaction. For the conjugate acid-base pair HA / A−, the ionization equilibrium equations and ionization constant expressions are
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Oligonucleotide conjugated multi-functional adeno-associated viruses.

Dhruva Katrekar1, Ana M Moreno1, Genghao Chen1

  • 1Department of Bioengineering, University of California, San Diego, CA, USA.

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Researchers engineered novel adeno-associated virus (AAV) vectors by attaching oligonucleotides to their surface. This innovation shields AAVs from neutralizing antibodies and enhances gene delivery capabilities.

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Area of Science:

  • Molecular Biology
  • Biotechnology
  • Gene Therapy

Background:

  • Recombinant adeno-associated viruses (AAVs) are widely used for in vivo gene delivery.
  • Limitations include restricted tropism and pre-existing neutralizing antibodies.
  • Engineering AAV capsid properties is crucial for improving gene delivery efficacy.

Purpose of the Study:

  • To develop multi-functional AAVs with programmable capabilities.
  • To engineer AAVs for enhanced gene delivery and protection against neutralizing antibodies.

Main Methods:

  • Genetically encoded incorporation of unnatural amino acids (UAAs) with bio-orthogonal handles onto AAV capsid proteins.
  • Site-specific conjugation of oligonucleotides to the AAV surface using click chemistry, creating oligo-AAVs.
  • Development of lipid-based cloaks for shielding oligo-AAVs from serum neutralization.

Main Results:

  • Successfully created sequence-specifically labeled and 2D-patterned oligo-AAVs.
  • Demonstrated effective shielding of AAV particles from neutralizing serum using lipid-based cloaks ('cloaked AAVs').
  • Confirmed 'cloaked AAVs' retained full functionality, including transduction of various cell types and delivery of CRISPR-Cas9.

Conclusions:

  • The developed programmable oligo-AAV system offers a versatile platform for AAV engineering.
  • This technology enhances AAV capabilities by enabling sequence-specific functionalities and protection against immune responses.
  • Anticipated broad utility in synthetic biology and advanced gene therapy applications.