Custom Morpholino Oligo

Based on our wide range of synthetic reagents and expertise in oligonucleotide characterization, BOC Sciences offers chemically synthesized and modified antisense oligonucleotides (ASOs) on different scales. All customized morpholino oligos we offer are produced under strict quality control standards to ensure 100% sequence identification.

What is Morpholino Oligo?

Morpholino oligo, also known as phosphorodiamidate morpholino oligo (PMO), is a short, single-stranded DNA analog containing a morpholine ring and a phosphorodiamidate backbone that replaces the 2'-deoxyribonucleoside and phosphate bonds of canonical DNA, respectively. Morpholino substitutions are six-membered rings that provide increased conformational rigidity when doped into the backbone of an oligonucleotide. Morpholino oligo has been extensively investigated as a potential spatial blocker for the treatment of a variety of hereditary disorders in oligonucleotide therapy due to its specificity, solubility, low toxicity, stability, and high efficiency.

Fig.1 Assembly of a Morpholino oligo containing the 5'-amine. (Moulton et al., 2017)

Mechanism of Action of Morpholino Oligo

When morpholino oligo specifically binds to the target site of its choice, it can block the binding of other cellular components to the target site, thus blocking the shearing of mRNA, and thus affecting the translation of proteins.

BOC Sciences' Morpholino Oligo Synthesis Services

BOC Sciences provides custom synthesis and chemical modification services for morpholino oligo to meet customers' needs for different sizes of morpholino oligo and also provides product optimization services.

• Customization of Morpholino Oligo

  
  The first step in the customization of morpholino oligo is the design of the sequence. According to the customer's needs and application, the specific gene and RNA regions of morpholino oligo are designed to ensure that they meet the customer's requirements. Subsequently, based on the characteristics of the designed morpholino oligo, our technicians will select the appropriate method for protocol design, product preparation and quality analysis. In the end, we will ensure that the product you obtain is highly pure and sequence-competitive.

• Chemical Modification of Morpholino Oligo

• Improving the membrane permeability

  
  Continuous improvement of morpholino oligo building blocks and chain synthesis methods is a prerequisite for morpholino oligo to move towards practical applications. Since the amino group on the terminal ring of morpholino oligo can act as a linkage handle, various chemical modifications such as the introduction of membrane-penetrating peptides, fluorescent groups, and photoswitching combinations can be performed using biocompatible linkage reactions. Reaction of the amino group with a carboxylic acid or carbonate to form the corresponding amide or carbamate group is the most preferred attachment strategy. Further functional groups, including reactive groups such as amino, carboxyl, sulfhydryl, alkynyl, and azide groups, can be introduced at the 3' and 5' ends of the morpholino oligo as connecting arms for further introduction of functional molecules. In addition, the modification of the structural unit of the morpholino can be carried out simultaneously, which is also aimed at improving the membrane permeability of the morpholino oligo.

• Other functional chemical modifications

  
  Other functional chemical modifications of morpholino oligo are mainly based on the introduction of various functional groups by Sonogashira, Suzuki and Heck coupling reactions, taking advantage of the ease of introducing halogen atoms at the 5-position of the pyrimidine base or the 8-position of the purine base.

• Combination with other nucleic acid modifications

  
  Combining morpholino oligo units with other nucleic acid modifications is a strategy to improve the drugability of nucleic acid drugs. For example, its introduction into various sites of siRNA can be screened for modifications that improve silencing effects and anti-enzymatic stability. Chimerization of morpholino monomers of thymine or guanine into the DNA sequence results in better antisense effects.

Applications of Morpholino Oligo

• Antisense Nucleic Acid Drugs

  
  Morpholino oligo targets no other antisense nucleic acid drug and can be used for anti-tumor, anti-viral, anti-bacterial and gene therapy of various systems of the body.

• Genetic Research Tools

  
  Knockdown of specific genes by using morpholino oligo's strong and durable binding to target RNAs provides an important tool for studying gene and protein function. At the same time, knockdown of specific genes allows us to assess their role in the response to toxic exposure and thus to understand the mechanisms of developmental toxicity at the molecular level.

Frequently Asked Questions (FAQ)

What factors affect the stability of morpholino oligos?

The stability depends on the sequence length, backbone modifications, and chemical functionalization, which influence resistance to enzymatic degradation and environmental conditions.

How can morpholino oligos be customized for improved cellular uptake?

Chemical modifications, such as attaching membrane-penetrating peptides or functional groups at the 3' or 5' ends, enhance membrane permeability without altering target specificity.

What methods are used to attach functional molecules to morpholino oligos?

Biocompatible linkage reactions, including amide or carbamate formation with terminal amino groups, enable conjugation of fluorescent labels, photoswitches, or reactive handles.

Can morpholino oligos be combined with other nucleic acid modifications?

Yes, integrating morpholino units with siRNA or DNA sequences improves binding specificity, enzymatic stability, and overall functional performance in research applications.

How is the sequence of a morpholino oligo determined for a specific application?

Sequence design is guided by the target RNA region and experimental goals, followed by computational analysis and synthesis optimization to ensure high specificity and competitive purity.

Reference

1. Moulton H M, et al. Morpholino oligomers[M]. Springer Science+ Business Media LLC, 2017.