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We have witnessed extensive research efforts to engineer AAV capsids for altered tropism
define tropism
Claude 4 Sonnet (T) via @hdevalence.bsky.social
Thinking Summary
The user is asking me to define "tropism" in the context of the article about adenoviruses and AAVs. Looking at the article, they mention tropism several times in relation to viral vectors and cell targeting. From the context in the article, tropism refers to which cells or tissues a virus preferentially infects or targets. The article explains this concept: "Which cells get transduced by the adenoviral capsid depends on its taxonomy, with different species and serotypes preferring different cell surface receptors for entry into the host. Species C adenoviruses, which include the adenovirus 5, use the coxsackie-adenovirus receptor (CAR), many species B use CD46 or desmoglein-2, while some other strains bind sialic acid. Because these receptors are patchily expressed, they dictate tropism." And later: "Adenovirus 5 chiefly targets the airway epithelium in the respiratory tract, yet the instant it meets blood it is hijacked." So tropism is about the natural targeting preference of viruses for specific cell types or tissues, determined by which receptors the virus uses to enter cells.
Tropism refers to the natural preference or affinity of a virus for infecting specific cell types or tissues.
In the context of viral vectors like AAV and adenovirus, tropism is determined by:
-
Receptor binding specificity - Different viruses bind to different cell surface receptors to gain entry
- Adenovirus 5 uses the coxsackie-adenovirus receptor (CAR)
- Some species B adenoviruses use CD46 or desmoglein-2
- Others bind sialic acid
-
Receptor distribution - Since these receptors are expressed differently across tissues, they "dictate tropism"
- CAR expression makes Ad5 naturally target respiratory epithelium
- But in blood, factor X hijacks Ad5 and redirects it to the liver
-
Therapeutic implications - Natural tropism may not align with therapeutic goals
- You want to deliver genes to specific diseased tissues
- But the virus may naturally prefer other cell types
- Hence the need to engineer "altered tropism" through capsid modifications
The article discusses how capsid engineering aims to redirect viral vectors away from their natural tropism toward therapeutically relevant targets - essentially reprogramming which cells the virus will infect and deliver its genetic cargo to.
This is why developing new capsid variants through directed evolution is so valuable - it can create vectors that target the specific tissues where gene therapy is needed, rather than where the virus would naturally go.