Jason T Kaelber
Rutgers University-New Brunswick, NJ·Biophysics
Gene therapies built on adeno-associated virus (AAV), a small harmless virus repurposed as a delivery shell for therapeutic genes, have reached the clinic, but they remain inefficient. Many particles travel all the way to the region just outside the cell nucleus and then stall, never releasing their genome where it must go.
- Fields
Biophysics
Microbiology & Immunology
Biochemistry
- Topics
adeno-associated virus
gene therapy
viral vectors
- Grants
- 1 known grant, through Jul 2030
What they work on
- Determine where and how the AAV genome exits the capsid by imaging perinuclear and intranuclear virions in infected cells with cryo-focused ion beam micromachining and electron tomography, plus an orthogonal optical method.
- Identify what distinguishes virions stalled outside the nucleus from those that successfully delivered their genome, comparing their structures and states along the infection pathway.
- Solve subnanometer-resolution structures of cell-attached AAV virions using ultrathin cells amenable to direct cryo-electron tomography, to clarify how the capsid engages its receptors.
- Perturb AAV genome packaging chemically and genetically to define its determinants, testing whether one intervention can increase the maximum transgene insert length a capsid will accept.
More about the research
That poor ratio of particles to successful deliveries forces very high clinical doses, which drives side effects and narrows the list of diseases AAV can treat. Limited control over which cell types are targeted and a cap on how much DNA a capsid can hold add further constraints. The molecular reasons behind each limitation have stayed obscure, largely because nobody could watch the relevant steps happen inside a cell.
Why it matters
Because most AAV particles fail to deliver their cargo, gene therapy patients receive enormous doses, which causes toxicity and keeps the approach off-limits for many conditions. Seeing exactly where delivery stalls, how capsids engage receptors, and what sets the packaging limit could guide redesign of AAV vectors toward higher efficiency, better targeting and larger therapeutic genes.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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Duke University, NC·Biomedical Engineering
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Willy Wriggers
Old Dominion University, VA·Biophysics
Develop measures of how well an atomic model fits local regions of a cryo-electron microscopy (cryo-EM) density map, and rate maps against reliable reference structures.
The school
Rutgers University-New Brunswick: 57 labs on PI Pages, $837M a year on research, 713 research doctorates a year.
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