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Principal Investigator: Li-Tao Guo
Organization: RNACONNECT INC
Fiscal Year: 2024
Award: $1,555,946
Funding agency: National Institute of General Medical Sciences
Summary
RNA is the central biomolecule of life, as it connects the sequence of DNA to the production of
proteins, and serves as a structural building block for critical components within the cell. Despite
the importance of detecting, quantifying and sequencing RNAs in order to exploit their roles in
biology and medicine, the field of RNA research remains limited by the tools available for
monitoring and manipulating RNA. An enzyme called reverse transcriptase (RT) is the most
foundational tool for converting RNA into cDNA, enabling sensitive detection and RNA
sequencing. However, existing, commercially available RTs have significant deficencies that
limit our ability to fully exploit them as engines for analysis and sequencing. This problem has
now been solved with the discovery of powerful new ultraprocessive RTs, MarathonRT (MRT)
and ultraMarathonRT (uMRT). Discovered by the Pyle Lab at Yale University, MRT is an
exceptionally processive RT that copies kilobase-length RNAs (such as the 30kb coronavirus
genome) in a single pass without inhibition by secondary structures or repeats within an RNA
template. Unlike other RTs, performance is maintained at ambient temperatures, which
eliminates RNA degradation and enables reagent kits that can be deployed without refrigeration.
For commercialization, the high-performance version, uMRT, will be developed, optimized and
incorporated into a suite of commercial products for mass distribution. This SBIR grant is
intended to fund the work necessary to create, develop, test and optimize these uMRT products
for the most common RT-PCR, qRT-PCR and sequencing applications. This grant will translate
an innovative scientific discovery into full-fledged commercial products that will significantly
improve research and clinical practice, underscoring the economic power of superior enzymatic
‘hardware.’
We will produce a family of products that boosts the sensitivity of RT-PCR and RNA sequencing
by employing a powerful new generation of reverse-transcriptase (RT) enzymes. History has
shown that innovation typically follows the creation of more powerful scientific tools, such as the
creation of the commercial biotechnology industry that followed the development of recombinant
DNA technology in the 1970s, or the emerging field of gene editing therapeutics following the
discovery of CRISPR enzymes. The introduction of uMRT products is a similar watershed
moment as the scientific community will, for the first time, be able to read and detect variation
within whole transcriptomes, revealing previously ‘invisible’ information that is critical for
understanding all layers of biological function, from patients to single cells.
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