IN SHORT
We can restore regular gene expression by preventing premature transcription termination.
Aptah's technology holds the potential to address different unmet medical needs by correcting a fundamental cell mechanism - the transcription machinery.
RNA WiCo™ - RNA Widespread Correction
At Aptah, we're pioneering a groundbreaking approach to combat age-related diseases:
Aptah Bio is working in the forefront of a novel technology called RNA WiCo™ (RNA Widespread Correction) able to edit, modulate and control the expression of different RNAs in a unique way.
Its lead compound (APT20TTMG) targets U1-snRNP which plays a crucial role in co-transcriptional gene regulation, extending transcription by preventing premature termination. This function is particularly important in ensuring full-length transcript synthesis known to be disturbed in many diseases.
It is the first drug designed to ensure the proper function of U1 complex, leading to the expression of widespread full-length 3′UTRs.
Results show the recovery of homeostatic protein expression, cell cycle, and a clear positive biological effect in different cell types and animal models. This therapy holds the potential to address a series of unmet medical needs, ranging from cancer, ophthalmology, autoimmune diseases and neurodegenerative diseases.
APT20TTMG does not silence any specific target, but rather works as a template for accurate RNA processing.
It does not change physiological alternative splicing and polyadenylation.
A Quick Overview:
A Four-Step Rationale
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Aging affects gene expression
RNA shortening leads to innumerous pathologies
Full length transcription elongation is crucial for healthy cells. Aging leads to an increasingly frequent and random gene length-dependent transcriptional decline.
Recently, researchers have identified the sporadic occurrence of premature cleavage and polyadenylation, which leads to a decrease in the expression of longer genes tightly linked with the function of specialised cells.
Data strongly suggests that widespread reductions in the 3′UTR of mRNAs are closely linked to the development of multiple sporadic diseases.
Ibañez-Solé; Barrio; Izeta, 2023. DOI: https://doi.org/10.1016/j.isci.2023.106368
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Aging affects RNA length
RNA shortening leads to innumerous pathologies
In the intricate world of genetic makeup, longer genes often encounter a greater risk of premature cleavage and splicing errors, paving the way for various diseases to manifest. Among these, neurodegenerative conditions, oncological challenges, metabolic imbalances, and ophthalmological ailments stand prominently. What's fascinating is the recurring pattern across diverse tissues and species, notably prevalent in individuals who have a history of smoking or sun exposure. This pattern also resonates deeply with those grappling with Alzheimer's disease and related afflictions. Such insights underscore the critical need for innovative solutions like ours, which aim to tackle these underlying genetic mechanisms, offering hope for improved health and longevity.
Ibañez-Solé; Barrio; Izeta, 2023. DOI: https://doi.org/10.1016/j.isci.2023.106368
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Our Target: U1 snRNP
U1 snRNPs (U1) regulates RNA transcription.
U1 snRNP is an essential component of the co-transcription splicing machinery. Pre-mRNA splicing and polyadenylation are crucial steps in mRNA maturation. Recent studies have shown that U1 snRNP also plays a global role in 3' end mRNA processing by preventing premature 3'-end cleavage and polyadenylation (PCPA), which is important for the full-length transcription of thousands of protein-coding and long noncoding genes.
Numerous studies have demonstrated abnormalities in U1 snRNP assembly and function in various sporadic diseases, including neurodegenerative & autoimmune diseases and various types of cancer.
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Our Target: U1 snRNP
U1 snRNPs (U1) regulates RNA transcription.
U1 snRNP is an essential component of the co-transcription splicing machinery. Pre-mRNA splicing and polyadenylation are crucial steps in mRNA maturation. Recent studies have shown that U1 snRNP also plays a global role in 3' end mRNA processing by preventing premature 3'-end cleavage and polyadenylation (PCPA), which is important for the full-length transcription of thousands of protein-coding and long noncoding genes.
Numerous studies have demonstrated abnormalities in U1 snRNP assembly and function in various sporadic diseases, including neurodegenerative & autoimmune diseases and various types of cancer.
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The Problem: U1 Disfunction
1. Interaction with RNA Polymerase II
U1 snRNP associates with RNA polymerase II (Pol II) during transcription, influencing its elongation efficiency. By suppressing premature PAS, U1 snRNP allows Pol II to continue elongation, effectively extending the transcription process.
2. Prevention of Premature Polyadenylation
U1 snRNP interacts with nascent pre-mRNA to suppress cryptic polyadenylation signals (PAS) that could prematurely terminate transcription. This function ensures that only the proper PAS at the 3' end of the gene is used for polyadenylation.
3. Implications in Long-Gene Expression
Genes with long transcription units (e.g., neuronal genes and lncRNAs) are particularly dependent on U1 snRNP to maintain full-length transcript synthesis.
4. U1 snRNP Disfunction
Loss of U1 snRNP function leads to truncated transcripts due to early transcription termination, leading to decreased expression of longer genes.
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The Problem: U1 Disfunction
1. Interaction with RNA Polymerase II
U1 snRNP associates with RNA polymerase II (Pol II) during transcription, influencing its elongation efficiency. By suppressing premature PAS, U1 snRNP allows Pol II to continue elongation, effectively extending the transcription process.
2. Prevention of Premature Polyadenylation
U1 snRNP interacts with nascent pre-mRNA to suppress cryptic polyadenylation signals (PAS) that could prematurely terminate transcription. This function ensures that only the proper PAS at the 3' end of the gene is used for polyadenylation.
3. Implications in Long-Gene Expression
Genes with long transcription units (e.g., neuronal genes and lncRNAs) are particularly dependent on U1 snRNP to maintain full-length transcript synthesis.
4. U1 snRNP Disfunction
Loss of U1 snRNP function leads to truncated transcripts due to early transcription termination, leading to decreased expression of longer genes.
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Our Technology:
RNA WiCo
RNA Widespread Correction
Our technology, represented by the lead compound APT20TTMG, restores regular gene expression and consequently the synthesis of multiple proteins by facilitating accurate U1 snRNP assembly.
This unique modulation-based compound is the result of advanced computer simulations and belongs to a new class of molecules.
APT20TTMG holds promise for addressing a wide range of sporadic genetic disorders by serving as a template for precise RNA processing without affecting physiological alternative splicing and polyadenylation.
| 4
Our Technology:
RNA WiCo
RNA Widespread Correction
Our technology, represented by the lead compound APT20TTMG, restores regular gene expression and consequently the synthesis of multiple proteins by facilitating accurate U1 snRNP assembly.
This unique modulation-based compound is the result of advanced computer simulations and belongs to a new class of molecules.
APT20TTMG holds promise for addressing a wide range of sporadic genetic disorders by serving as a template for precise RNA processing without affecting physiological alternative splicing and polyadenylation.
OUR PIPELINE
WHY APTAH
Current technologies are unable to address the great majority of diseases due to their multifactorial aspect and lack of etiology understanding.
About 90% of diseases are sporadic, meaning they are not associated with inherited genetic mutations. However, their etiology remains a long-standing question for scientists.
While many diseases share fundamental biological processes necessary for their development and progression, they also differ in their reliance on specific pathways. In recent years, targeted therapies have been introduced with varying degrees of success. However, single-targeted therapies may only be effective for certain types of diseases and may not address malignancies that rely on multiple pathways, a common aspect in sporadic diseases.
OUR TEAM & LEADERSHIP
Marcelo do O
Chief Business Officer
Juliana M. Bottos, MD PhD
Scientific Advisory Board | Ophthalmology
Prof. George Church
Scientific Advisory Board
Dieter Weinand, MBA
Chairman of the Board
Rafael Bottos
Co-Founder & CEO
Caio Bruno Leal
Co-Founder & CSO
Camila Zimmer, PhD
Head of Preclinical Studies
Vanessa Sinatti, PhD
Head of Bioinformatics
Jonas Sister
Business Development
João Camargo
CFO
Jaudir Caetano da Silva
Head of CMC
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Ericks Sousa, PhD
Biochemistry
OUR PARTNERS
