A critical analysis of codon optimization in human therapeutics.

Area of Science:

• Biotechnology
• Molecular Biology
• Genetic Engineering

Background:

• Codon optimization is a gene engineering technique that modifies synonymous codons to enhance protein production.
• It is widely applied in developing recombinant protein drugs and nucleic acid therapies like gene therapy, mRNA therapy, and DNA/RNA vaccines.

Purpose of the Study:

• To critically review the potential hazards and challenges associated with codon optimization.
• To evaluate its impact on protein conformation, function, immunogenicity, and overall efficacy, particularly in nucleic acid therapies.

Main Methods:

• Literature review and critical analysis of existing reports on codon optimization.
• Examination of potential risks, including those unique to nucleic acid-based therapeutics.

Main Results:

• Codon optimization can negatively affect protein conformation and function.
• It may increase immunogenicity and reduce the efficacy of biotech therapeutics.
• Specific risks are associated with its application in nucleic acid therapies.

Conclusions:

• The scientific basis for codon optimization is challenged by its evolved complexity.
• Codon optimization may not be the optimal strategy for increasing protein production and can decrease therapeutic safety and efficacy.
• Reconsideration of this approach, especially for in vivo applications, is recommended.