PMO-based Core Chemistry
While PMOs have the same nucleic acid bases naturally found in RNA or DNA (i.e. adenine, cytosine, guanine, uracil or thymine), they are bound to morpholine rings instead of the ribose rings used by RNA. They are also linked through phosphorodiamidate rather than phosphodiester or phosphorothioate groups. This linkage modification eliminates ionization in the usual physiological pH range, so PMOs in organisms or cells are uncharged molecules. The entire backbone of a PMO is made from these modified subunits.
| Property | Traditional Antisense |
siRNA | AVI’s PMO Chemistries |
| Efficacy: Ability to target specific genetic sequences without risk of non-specific immunomodulation effects |
— | — | ✓ |
| Safety: Excellent safety profile preclinically and clinically up to high doses |
— | — | ✓ |
| Distinct Mechanisms of Action: Ability to modulate gene expression, including up-regulation of gene expression |
— | — | ✓ |
| Delivery: Expanded flexibility allowing chemical modification for specific tissue and pathogen targeting |
— | — | ✓ |
| Stability: Resistant to enzymatic degradation in vivo |
— | — | ✓ |
We believe these key differences provide our RNA therapeutic candidates with pharmaceutical properties that are preferable to achieve broader drug characteristics and greater potential clinical utility than the other antisense compounds.
Proprietary, AVI, Advanced Generation PMO-Based Chemistries
AVI has dedicated significant resources to the development of advanced generation RNA-based antisense chemistries with superior drug-like performance characteristics. This investment has been very productive and we are currently applying several novel and proprietary PMO based platform chemistries to the discovery and development of new drug candidates. Specifically, we have advanced our foundational PMO chemistry through the construction of a series of novel and proprietary PMO-based platforms.
PPMOs
AVI has developed a proprietary technology of peptide conjugated phosphorodiamidate morpholino oligomers, or our PPMO platform. Using our PPMO technology, cellular uptake of the active PMOs, as well as their potency and specificity of tissue targeting, are significantly enhanced by the conjugation of arginine-rich cell-penetrating peptides (CPPs) chemical moieties to a PMO.
PMOplus™
Another proprietary analogue platform, our PMOplus™, uses the addition of positionally specific molecular charges into the PMO backbone. This is intended to specifically enhance drug performance characteristics on two key parameters: targeted cell penetration, and the maintenance of antiviral performance in the presence viral mutation.
PMO-X
AVI’s most recent advance in chemistry, PMO-X, is focused on the incorporation of new proprietary chemical technology to fine-tune important physicochemical properties, intended to enhance in vivo tissue targeting, selectivity, and potency. The intrinsic neutral structure of the PMO provides continuing opportunities to create innovative and potentially transformative RNA-based therapeutics with varied beneficial properties.
We are researching additional chemistry advances to further optimize our core proprietary technology platforms as well as to develop further novel analogues that we believe could provide beneficial characteristics, such as potency, bioavailability, therapeutic index and tissue selectivity, to our drug candidates.
This page was last updated on July 8, 2010.
