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How to construct an „ultimate“ viral vector for molecular therapies?

Image credit: Andre Pelzmann

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Andre Pelzmann
Andre Pelzmann Nov 25, 2020
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Necessity

Is the problem still unsolved?

Conciseness

Is it concisely described?

Currently one of the most important problems of innovative genome engineering is effective in vivo intracellular delivery of the tissues of interest. All of the common vectors have their limitations. However, now we could theoretically create an artificial „designer“ vector which could alloy the best natures of the conventional vectors by the approach of synthetic virology ( a relatively new discipline at the intersection of virology, computational biology, synthetic biology, and DNA nanotechnology) Lets set aside from other, non-viral drug-gene delivery opportunities in this case.

The common vectors are:

Adeno-associated Virus AAV:
insert size limit of 4.5kb, requirement of adenovirus or herpes virus for AAV replication, low transduction efficiency, difficult generation of high titers

Poxvirus:
possible cytopathic effects

Herpes Virus:
possible toxicities, risk of recombination

Adenovirus:
transient gene expression, an immune response to viral proteins, insert size limit of 7,5 kb

Retroviral vectors:
transfect only proliferating cells, a concern of insertional mutagenesis, a difficult target of viral infection

Lentiviral vectors:
potential insertional mutagenesis


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