Critical considerations for developing nucleic acid macromolecule based drug products

Muralidhara, B. K.; Baid, Rinku; Bishop, Steve M.; Huang, Min; Wang, Wei; Nema, Sandeep

doi:10.1016/j.drudis.2015.11.012

Cited by 41 publications

(22 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RNA is susceptible to degradation by both enzymatic and chemical pathways 157 . Formulation buffers are tested to ensure that they are free of contaminating RNases and may contain buffer components, such as antioxidants and chelators, which minimize the effects of reactive oxygen species and divalent metal ions that lead to mRNA instability 159 .…”

Section: Therapeutic Considerations and Challengesmentioning

confidence: 99%

mRNA vaccines — a new era in vaccinology

Pardi

Hogan

Porter

et al. 2018

Nat Rev Drug Discov

3,275

3,330

View full text Add to dashboard Cite

mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.

show abstract

Section: Therapeutic Considerations and Challengesmentioning

confidence: 99%

mRNA vaccines — a new era in vaccinology

Pardi

Hogan

Porter

et al. 2018

Nat Rev Drug Discov

3,275

3,330

View full text Add to dashboard Cite

show abstract

“…The mRNA drug substance and formulated drug product undergo testing and in-process analytics to assess identity, appearance, content, integrity, residual DNA, endotoxin contamination, and sterility. 40 A potency test is used to verify the ability of the mRNA to be translated into a desired protein product after delivery into target cells. Depending on the specific mRNA construct, the abovedescribed procedure may be slightly modified to accommodate modified nucleosides, capping strategies, or purification protocols.…”

Section: Cell-free Production and Purification Of Mrna Vaccinesmentioning

confidence: 99%

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

et al. 2019

View full text Add to dashboard Cite

“…Common attributes of nucleic acid drugs such as high molecular weight, negatively charged nature, and susceptibility to degradation by nucleases severely restricts their delivery. Consequently, these nucleic acid molecules exhibit limited bioavailability in their naked form, and face challenges from formulation to their “successful delivery” at the targeted site and cell . An effective and safe delivery system is a prerequisite to realize clinical translation of these therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Development of “CLAN” Nanomedicine for Nucleic Acid Therapeutics

Iqbal

Shen

et al. 2019

Small

View full text Add to dashboard Cite

Nucleic acid‐based macromolecules have paved new avenues for the development of therapeutic interventions against a spectrum of diseases; however, their clinical translation is limited by successful delivery to the target site and cells. Therefore, numerous systems have been developed to overcome delivery challenges to nucleic acids. From the viewpoint of clinical translation, it is highly desirable to develop systems with clinically validated materials and controllability in synthesis. With this in mind, a cationic lipid assisted PEG‐b‐PLA nanoparticle (CLAN) is designed that is capable of protecting nucleic acids via encapsulation inside the aqueous core, and delivers them to target cells, while maintaining or improving nucleic acid function. The system is formulated from clinically validated components (PEG‐b‐PLA and its derivatives) and can be scaled‐up for large scale manufacturing, offering potential for its future use in clinical applications. Here, the development and working mechanisms of CLANs, the ways to improve its delivery efficacy, and its application in various disease treatments are summarized. Finally, a prospective for the further development of CLAN is also discussed.

show abstract

Critical considerations for developing nucleic acid macromolecule based drug products

Cited by 41 publications

References 102 publications

mRNA vaccines — a new era in vaccinology

mRNA vaccines — a new era in vaccinology

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

Development of “CLAN” Nanomedicine for Nucleic Acid Therapeutics

Contact Info

Product

Resources

About