Target selection
Disease-associated transcripts are analyzed to identify the optimal Kozak sequence for therapeutic modulation, while preserving endogenous gene regulation.
Our Science
Engineering protein expression with precision
Our Science
Engineering protein expression with precision
THE CHALLENGE
When disease is a matter of dosage
Many genetic disorders do not arise because a protein is completely absent, but because cells produce it at the wrong level. In haploinsufficient disorders, the loss of one functional gene copy reduces protein production below the threshold required for normal physiology. Conversely, excessive protein expression can also disrupt cellular homeostasis and contribute to disease.
Current therapeutic strategies often rely on replacing defective genes or suppressing harmful ones. While highly effective in specific contexts, these approaches generally provide an “on-or-off” solution to a problem that frequently requires fine adjustment.
THE CHALLENGE
When disease is
a matter of dosage
Many genetic disorders do not arise because a protein is completely absent, but because cells produce it at the wrong level. In haploinsufficient disorders, the loss of one functional gene copy reduces protein production below the threshold required for normal physiology. Conversely, excessive protein expression can also disrupt cellular homeostasis and contribute to disease.
Current therapeutic strategies often rely on replacing defective genes or suppressing harmful ones. While highly effective in specific contexts, these approaches generally provide an “on-or-off” solution to a problem that frequently requires fine adjustment.
SCIENTIFIC FOUNDATION
Translation begins at the Kozak sequence
Protein synthesis starts when the ribosome recognizes the translation initiation site on messenger RNA. One of the key determinants of this process is the Kozak sequence, a short nucleotide motif surrounding the AUG start codon.
Although discovered more than forty years ago, the Kozak sequence has traditionally been viewed as a passive regulatory element. Recent research has instead revealed that naturally occurring differences in Kozak strength substantially influence how efficiently proteins are produced.
This insight opened an entirely new therapeutic opportunity: rather than replacing genes, it may be possible to restore physiological protein levels simply by optimizing translation initiation.
SCIENTIFIC FOUNDATION
Translation begins
at the Kozak sequence
Protein synthesis starts when the ribosome recognizes the translation initiation site on messenger RNA. One of the key determinants of this process is the Kozak sequence, a short nucleotide motif surrounding the AUG start codon.
Although discovered more than forty years ago, the Kozak sequence has traditionally been viewed as a passive regulatory element. Recent research has instead revealed that naturally occurring differences in Kozak strength substantially influence how efficiently proteins are produced.
This insight opened an entirely new therapeutic opportunity: rather than replacing genes, it may be possible to restore physiological protein levels simply by optimizing translation initiation.
FROM DISCOVERY TO PLATFORM
From academic discovery to BOOST 2.0
Haploinsufficient genes screened
+
0
Editable Kozak variants evalueted
+
0
Translation-enhancing variants identified
0
BOOST originated from years of research at the University of Trento, where Professor Alessandro Quattrone’s laboratory explored how subtle changes within the Kozak sequence influence translation efficiency and ultimately determine protein dosage.
By systematically analyzing hundreds of human haploinsufficient genes and thousands of editable Kozak variants, the team identified naturally occurring regulatory sequences capable of enhancing protein translation through precise nucleotide modifications. These studies demonstrated that translation initiation itself could become a therapeutic target rather than simply a biological process.
The original BOOST approach provided the first proof of concept that targeted optimization of the Kozak sequence could restore physiologically relevant protein levels in cellular models of haploinsufficiency using CRISPR base editing.
FROM DISCOVERY TO PLATFORM
From academic discovery to BOOST 2.0
Haploinsufficient genes screened
+
0
Editable Kozak variants evalueted
+
0
Translation-enhancing variants identified
0
BOOST originated from years of research at the University of Trento, where Professor Alessandro Quattrone’s laboratory explored how subtle changes within the Kozak sequence influence translation efficiency and ultimately determine protein dosage.
By systematically analyzing hundreds of human haploinsufficient genes and thousands of editable Kozak variants, the team identified naturally occurring regulatory sequences capable of enhancing protein translation through precise nucleotide modifications. These studies demonstrated that translation initiation itself could become a therapeutic target rather than simply a biological process.
The original BOOST approach provided the first proof of concept that targeted optimization of the Kozak sequence could restore physiologically relevant protein levels in cellular models of haploinsufficiency using CRISPR base editing.
HOW IT WORKS
How BOOST 2.0 works
01
02
BOOST design
BOOST 2.0 is engineered to selectively recognize the target regulatory sequence responsible for controlling translation initiation.
03
Translation modulation
Interaction with the Kozak sequence fine-tunes ribosome recruitment, precisely adjusting protein synthesis without altering the genomic DNA.
04
Protein restoration
Protein production is restored toward its physiological range, aiming to recover normal cellular function through endogenous regulation.
HOW IT WORKS
How BOOST 2.0 works
01
Target selection
Disease-associated transcripts are analyzed to identify the optimal Kozak sequence for therapeutic modulation, while preserving endogenous gene regulation.
02
BOOST design
BOOST 2.0 is engineered to selectively recognize the target regulatory sequence responsible for controlling translation initiation.
03
Translation modulation
Interaction with the Kozak sequence fine-tunes ribosome recruitment, precisely adjusting protein synthesis without altering the genomic DNA.
04
Protein restoration
Protein production is restored toward its physiological range, aiming to recover normal cellular function through endogenous regulation.
PLATFORM ADVANTAGES
Why BOOST 2.0 is different
ENDOGENOUS REGULATION
BOOST 2.0 acts on the endogenous gene, preserving native regulatory mechanisms and maintaining the physiological genomic context.
PRECISION MODULATION
Instead of binary gene activation or silencing, BOOST 2.0 enables fine-tuning of protein production within a therapeutically relevant range.
ONE MECHANISM, MULTIPLE MUTATIONS
Many rare genetic diseases are caused by haploinsufficiency. BOOST 2.0 enhances expression of the remaining healthy copy, offering a mutation-agnostic approach with broad therapeutic potential.
PLATFROM VERSATILITY
By targeting a universal mechanism of translation initiation, BOOST 2.0 establishes a versatile platform that can be adapted across multiple dosage-sensitive genetic disorders.
PLATFORM ADVANTAGES
Why BOOST 2.0 is different
ENDOGENOUS REGULATION
BOOST 2.0 acts on the endogenous gene, preserving native regulatory mechanisms and maintaining the physiological genomic context.
ONE MECHANISM, MULTIPLE MUTATIONS
Many rare genetic diseases are caused by haploinsufficiency. BOOST 2.0 enhances expression of the remaining healthy copy, offering a mutation-agnostic approach with broad therapeutic potential.
PRECISION MODULATION
Instead of binary gene activation or silencing, BOOST 2.0 enables fine-tuning of protein production within a therapeutically relevant range.
PLATFROM VERSATILITY
By targeting a universal mechanism of translation initiation, BOOST 2.0 establishes a versatile platform that can be adapted across multiple dosage-sensitive genetic disorders.