Related Experiment Video
Updated: Jul 10, 2026
08:14
Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Breaking the bonds: non-viral vectors become chemically dynamic
1Waisman Center, Department of Pediatrics and Medical Genetics, University of Wisconsin-Madison, Madison, Wisconsin, USA. jwolff@wisc.edu
Summary
Chemically dynamic synthetic vehicles improve nucleic acid delivery by using masked endosomolytic agents (MEAs). These agents release their payload in response to the endosomal environment, enhancing therapeutic potential for plasmid DNA (pDNA) and small interfering RNA (siRNA).
Area of Science:
- Biotechnology
- Molecular Biology
- Drug Delivery
Background:
- Nucleic acid delivery (plasmid DNA, siRNA) is crucial for research and therapeutics.
- Non-viral synthetic vehicles (SVs) like lipoplexes and polyplexes are common delivery methods.
- Improving SV efficacy requires dynamic systems responsive to physiological cues.
Purpose of the Study:
- To develop chemically dynamic synthetic vehicles for enhanced nucleic acid delivery.
- To utilize masked endosomolytic agents (MEAs) for improved endosomal escape.
- To achieve efficient in vivo delivery of nucleic acids.
Main Methods:
- Design of SVs with chemically labile bonds.
- Incorporation of pH-sensitive masked endosomolytic agents (MEAs).
- Evaluation of MEA-containing dynamic polyconjugates (DPCs) for in vivo siRNA delivery.
Main Results:
- MEAs, when exposed to acidic endosomal environments, release their endosomolytic function.
- Dynamic polyconjugates (DPCs) incorporating MEAs demonstrated efficient in vivo siRNA delivery to hepatocytes.
- Labile bonds enable controlled release and prevent premature MEA activation.
Conclusions:
- Chemically dynamic SVs with masked endosomolytic agents offer a promising strategy for nucleic acid delivery.
- This approach balances efficient in vivo delivery with effective endosomal escape.
- The design allows for targeted release into the cytoplasm, improving therapeutic outcomes.
Related Concept Videos
01:19Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
00:57Viral Recombination
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
00:36Viral Mutations
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
01:25Inhibitors Of Virion Release
Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
01:26DNA Bacteriophages
Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
01:10Retrovirus Life Cycles
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...