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Related Concept Videos

Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.

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Developing Stapled Aptamers with a Constrained Conformation for Osteogenesis Imperfect Therapeutics.

Gubu Amu1,2, Ge Zhang3,4, Nannan Jing5

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A new aptamer stabilization strategy enhances affinity and stability, showing promise for treating osteogenesis imperfecta by boosting bone growth. This method improves therapeutic potential for aptamer-based drugs.

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Area of Science:

  • Biotechnology
  • Drug Development
  • Molecular Biology

Background:

  • Aptamers show therapeutic promise but face challenges due to instability, impacting affinity, serum stability, and potency.
  • Limited clinical translation of aptamers stems from difficulties in stabilizing their conformation for therapeutic use.

Purpose of the Study:

  • To develop a feasible strategy for stabilizing aptamers by creating stapled aptamers.
  • To evaluate the therapeutic potential of stabilized sclerostin aptamers in an osteogenesis imperfecta mouse model.

Main Methods:

  • Utilized predicted binding conformations and titration cross-linking (TTC) to synthesize stapled aptamers.
  • Assessed the affinity and serum stability of stapled aptamers.
  • Tested the efficacy of a stapled sclerostin aptamer (c-0127OA) in a mouse model of osteogenesis imperfecta.

Main Results:

  • Successfully synthesized stapled sclerostin aptamers with over 70% yield.
  • Stapled aptamers exhibited a 20-fold increase in affinity and negligible degradation within 32 hours.
  • The stapled aptamer c-0127OA demonstrated potent sclerostin antagonism and enhanced bone anabolic potential in mice.

Conclusions:

  • The developed aptamer stapling strategy effectively stabilizes aptamer conformation.
  • Stapled aptamers offer improved therapeutic properties, including enhanced affinity and stability.
  • c-0127OA is a promising therapeutic candidate for osteogenesis imperfecta, warranting further clinical investigation.