The contemporary sphere of oncological therapeutics has witnessed a phenomenal shift in methodology, pivoting from conventional treatment modalities to exploring and utilizing the power of biological entities, notably viruses. Oncolytic virotherapy stands as an avant-garde dissertation in this evolution. It is predicated on the judicious fabrication of Oncolytic Viruses (OVs), biological entities ingeniously engineered to detect, invade, and obliterate cancerous cells while sparing healthy cells unscathed. This article aims to illuminate the intricate process of Oncolytic Virus creation and arm readers with insights into this burgeoning domain within biomedical research.

OVs are emblematic of Nature's paradoxical duality - entities known as the harbingers of disease are now repurposed as vanguards in the battle against cancer. Transforming a pathogen into a potential cure requires a meticulous understanding of viral morphology, functionality, and manipulation principles that govern the genetic framework.

Oncolytic Viruses are wrought using an array of techniques, each technique contingent on the virus strain and the cancer form it targets. It is essential to curate a virus capable of adeptly identifying and effacing cancer cells.

Among the pantheon of techniques are 'transduction' and 'transfection', both circumscribing the introduction of foreign DNA to replicate the virus within the host. Transduction, involving vectors, typically retroviruses or lentiviruses, introduces the curative genetic material into the host cell. Conversely, transfection employs other means – viral/bacterial plasmids, liposomes, etc. – to permeate the cell membrane and deposit the therapeutic gene.

Post transfection or transduction, the ‘armed’ virus proliferates within the cancer cell, causing its lysis, and is then primed to infect other adjacent malignant cells, prompting an exponential eradication of the tumorous growth.

The selection of the virus itself is a cornerstone in OV creation. Viruses commonly employed range from Herpes Simplex Viruses (HSVs), Coxsackieviruses, Reoviruses to the Vaccinia virus, chosen primarily for their proclivity to target specific types of cancer cells, and their unique ability to engender an immune response.

The genetic manipulation of these viruses is often proposed to enhance safety and efficiency. Common engineering strategies involve deletion or mutation of key viral genes, restricting the virus’s ability to replicate solely within cancer cells.

Another sophisticated strategy is called 'Arming the Virus', using it as a transport mechanism to deliver genes encoding immune modulatory agents or antiangiogenic molecules. This multifaceted approach enhances the cytolytic effect of the virus against the cancer cell, while concurrently sensitising the immune system to the presence of cancer antigens, thus provoking a potent immune response.

Despite the progress, creating safe, effective OVs poses substantial challenges. Key issues span attaining high cancer selectivity, mitigating potential off-target effects and immune responses, countering pre-existing immunity to some viruses, and circumventing the malignant tumor's physical barriers.

However, with continuous innovations and evolving comprehension of viral biology and cancer physiology, the day is not far when oncolytic virosurgery will be a standard therapeutic approach against cancer. This cutting-edge therapeutic modality provides an extraordinary beacon of potential for the intractable predicament of cancer, illuminating a path towards a future where resistance may indeed be futile—for cancer.