Molecular brush-conjugated antisense oligonucleotide as a pan-kras depletion agent
Ended Project Grant Awarded Last action
- Award ID
- R42CA275425
- Recipient
-
Pacdna LLC UEI DPEMWHCURCR5
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,983,054
Award facts
- Assistance listing
- 93.395 Cancer Treatment Research
- Completion date
- Originally
- Place of performance
- Massachusetts, USA
Award details come from USAspending.gov.
Description
- Abstract
- Mutant forms of kras are a key driver in human tumors but remain partially refractory to therapeutic intervention. After over three decades of research, only a single inhibitor (sotorasib) targeting a single mutation (KRASG12C) have reached market. The difficulty for developing small molecule kras inhibitors has heightened the importance of alternative methods targeting the oncogene. One such strategy involves therapeutic nucleic acids, which make IT possible to deplete target proteins that are intractable to conventional drug modalities. We have developed a novel form of nucleic acid therapeutics, termed brushield™ conjugate, which substantially enhances the antitumor activity of antisense oligonucleotides by elevating in vivo stability, accelerating cellular uptake, and improving plasma pharmacokinetics and tumor accumulation, allowing for a much lower dosage to be used compared to conventional methods. The conjugate also suppresses nearly all side effects associated with traditional nucleic acid drugs by reducing unwanted nucleic acid-protein interactions. The goal of this proposal is to lay the groundwork for translating the technology towards the clinic. In phase i, we will optimize the structure of the brushield™ conjugate, and enhance current indication using a panel of non-small cell lung cells and mouse xenograft models. Upon reaching set quantitative milestones, we will subject the conjugate to more relevant animal models (orthotopic and patient-derived xenograft models), and perform tolerability and pharmacokinetic studies in mice and monkeys (phase II). These studies will allow US to pursue an IND filing at the end of the project.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $988,000 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $30,054 | |
| Amendment | $1,000,000 | |
| Amendment | $1,000,000 | |
| Amendment | $55,000 | |
| Amendment | $55,000 | |
| Amendment | $55,000 | |
| Amendment | $400,000 | |
| Original award | $400,000 |
Show all 12
Quick answers
Who received award R42CA275425?
R42CA275425 was awarded to Pacdna LLC by National Cancer Institute (National Institutes of Health) on September 1, 2022.
How much is award R42CA275425 worth?
$3,983,054 has been obligated on R42CA275425.
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