Next Generation AAV Vector Technology
Lacerta Therapeutics is combining rational and combinatorial methodologies in a state of the art AAV technology platform capable of directed evolution of novel capsid variants possessing selective vector characteristics. Depending on the selection pressure applied, the Lacerta Therapeutics approach allows for the development of novel AAV vectors with improved transduction, tissue- or cell subtype-selectivity, and immune escape profiles from a single highly complex library derived from any of the naturally occurring serotypes.
The Lacerta Therapeutics AAV library strategy has the following advantages over other combinatorial approaches:
- Our strategy results in capsid libraries that are logs better in complexity than less sophisticated, shuffled serotype libraries
- Our strategy involves pre-selection for 3D compatibility using insight gained from thorough analysis of AAV structural characteristics and target only capsid variable regions (VRs) to combine mutagenesis and evolution in a unified approach
OneBac AAV Manufacturing Platform
A major hurdle to the broad application of AAV vectors to treat large clinical indications is the lack of a robust, scalable production platform. Industry-wide, much effort is being placed on the development of vector manufacturing platforms that ultimately will be insufficient to provide yields capable of supporting large clinical trials or in disease indications where commercial demand may make many of the current manufacturing systems obsolete. Moreover, many of the current systems require multiple, open manipulations, thus raising the risk of potential contamination of cultures and loss of clinical vector material.
Lacerta Therapeutics' OneBac insect cell based production platform has many advantages over other vector production systems including:
- Limited production components
- Sf9 stable cell lines capable of growth in suspension to high volumes and cell densities
- Robust AAV yields following infection with single, stable baculovirus expressing the disease specific transgenes
Taken together, the Lacerta Therapeutics OneBac vector production platform significantly reduces overall cost of goods while generating high yield, quality AAV vector preparations.
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